Postoperative Correlation of Radiological and Surgical Findings in Management of Ethmoid Sinus Adenocarcinoma

Patients and methods: A retrospective, monocentric study was carried out including all patients diagnosed with ADK who underwent surgery and were followed up at our center between 2012 and 2016 and who were monitored postoperatively using magnetic resonance imaging (MRI) and histopathological verifi cation of suspicious areas identifi ed via imaging. Time to postoperative MRI, time to recurrence and sites of recurrence were obtained for each patient.


Introduction
Paranasal sinus and nasal fossa cancers are rare tumors which are found most commonly in the ethmoid sinuses (5 % -30%) [1,2]. Adenocarcinoma of the ethmoid sinus (ADK) is the prevailing histological type and originates in the olfactory cleft [1][2][3][4]. Prognosis of this type of neoplasia is essentially determined by initial local control of the disease.
Despite recent innovations in such treatment (quality of Abstract Aims: Prognosis of ethmoid sinus adenocarcinoma (ADK) is essentially determined by local tumor control. There is a high rate of recurrence of these tumors across the range of patient series. Development of an optimal follow-up protocol of such tumors is recommended.

Patients and methods:
A retrospective, monocentric study was carried out including all patients diagnosed with ADK who underwent surgery and were followed up at our center between 2012 and 2016 and who were monitored postoperatively using magnetic resonance imaging (MRI) and histopathological verifi cation of suspicious areas identifi ed via imaging. Time to postoperative MRI, time to recurrence and sites of recurrence were obtained for each patient.
Objectives: Performance evaluation of MRI in early screening of recurrence or residualtumors postoperatively in the management of ADK and identifi cation of the main sites prone to risk of recurrence in these tumors.

Results:
We included 24 cases of ADK, there were 33% cases of recurrence with a mean time to recurrence of 35 months postoperatively. Mean time to completion of the fi rst MRI scan was 65 days postoperatively.
Conclusions: Effi cacy of postoperative MRI screening appears to be limited and regular endoscopic monitoring associated with imaging is required. Sites prone to risk should be subject to particular consideration in primary surgical resection and management of recurrence.
The benefi t of imaging in the immediate postoperative period has yet to be assessed in terms of disease-free survival and disease control. endoscopic optics, endonasal instrumentation, intensitymodulated conformal radiotherapy…) clinical evolution nevertheless demonstrates a high rate of locoregional recurrence (30% of cases on average) involving complications principally due to complex anatomy and proximity to important anatomic structures [11][12][13].
Tumors are predominantly monitored using magnetic resonance imaging (MRI) and endoscopic examination under local anesthetic by appointment and/or general anesthetic involving biopsy in the event of the slightest doubt.
This study aims i) to evaluate the benefi t of the fi rst postoperative MRI in detecting tumor recurrence ii) to determine its benefi t in surgical management of recurrence iii) to identify the main sites prone to risk of recurrence.

Patients and Methods
We carried out a retrospective monocentric study on 24 patients (n=24) treated in our center for primitive ADK during the period from 2012 to 2016. Inclusion criteria comprised all cases of initial or recurrent primitive ADK having undergone surgical resection followed by MRI monitoring (indifferently 1,5 or 3 Tesla, depending on the availability of the devices on the date of follow-up) and histological confi rmation of suspicious areas detected on imaging.
We excluded i) all primitive ethmoid sinus tumors which were not adenocarcinomas ii) tumors which did not receive postoperative MRI monitoring.
For each patient we recorded the gender, age, incidence of occupational exposure to risk, initial loco-regional extension of the tumor shown on imaging, initial evidence of lymphadenopathy, TNM stage, initial treatment, selection of surgical approach (endonasal or external), presence of treatment adjuvant to surgery, delivered dose and delivery duration involving external radiotherapy, type of chemotherapy, period of time before completion of postoperative MRI, incidence of recurrence including site of recurrence and time to recurrence, treatment of recurrence, follow-up time in relation to initial treatment.
All of the MRI scans were assessed by a single experienced radiologist who was blind to subject status and specialised in ENT and facial bone imaging.

Radiological
interpretation was compared with anatomopathological results of biopsies performed in suspicious areas, thus determining statistical measures of sensitivity (Se), specifi city (Sp), negative predictive value (NPV) and positive predictive value (PPV).

Postoperative MRI
The fi rst postoperative follow-up MRI scan was performed at a mean of 65 days after surgical resection (median 50 days) with a progressive decrease in interval length over a period of years [ Figure 1].
During follow-up of our 24 patients, 32 initial postoperative imaging scans were performed following initial surgery or secondary surgery for recurrence. Of the 32 imaging scans, CISPLATIN-based radio-chemotherapy 12.5% (n=1). *CISPLATIN: 2 patients for premature local recurrence (before the beginning of radiotherapy) particularly aggressive of impossible excision ** 4 very early stages with complete excision and compliant to the clinico-radiological follow-up (REFCOR reference), a patient in view of the general condition and a patient for personal preference ***5-FU applied topically on nasal packs inserted at the end of the procedure during initial surgery (solely for use in T4 in the absence of further objective criteria at our disposal, specifi cally this indication does not depend on positive or negative frozen section results). ****Lymph node recurrence several months after local recurrence: local recurrence 15 months after initial surgery with lymph node recurrence at 17 months in one case and local recurrence at 118 months with lymph node recurrence at 184 months in another case.
41% (n=13/32) showed suspicious images evoking recurrence. 69% (n=9) of the suspicious fi ndings in these 13 MRI scans had suspicion of recurrence confi rmed histopathologically and 5 cases of recurrence were observed following an initial postoperative MRI scan which appeared unremarkable (Se 64%; Sp 78%; PPV 69%; NPV 74%). In the 8 patients with recurrence, 17 immediate postoperative follow-up MRI scans were indicative of recurrence. The main sites of recurrence detected are shown in Figure 3.

Discussion
Current treatment of ADK is based on surgical resection followed by adjuvant radiotherapy. Rates of local recurrence remain high in the literature [5,7,8,11,14].
Within this context patient follow-up proves to be a key element in the treatment of these rare tumors.
Patient monitoring consists primarily of MRI scans and endoscopic evaluation although the exact methods involved have not been clearly defi ned [15].
Our retrospective monocentric study evaluates the performance of initial postoperative imaging in early detection of recurrence or of the progressive course of these tumors after surgery and the principal sites prone to risk.
Rates of recurrence in our population correspond to those found in the literature [ Table 2].
De Gabory et al. [11] in their 2010 study detected a mean recurrence rate involving ADK of 30% in the literature, in accordance with that of our study.
The low recidivism rates found in recent studies by Vergez et al. [14] (17.6%) and Nicolai et al. [8] (21.3%) compared with the common literature (30% on average) and in our study (33.3%) can be explained in part by the presence of smaller populations in their populations of advanced tumor stages (26.1% % Of tumors classifi ed T4 for Vergez and al., 32% of T4 tumors for Nicolai and al., 37.5% in our population). The tumor recurrence rate thus appears to be directly correlated with the initial stage of the tumor, the authors with the lowest recurrence rate being those with the least number of advanced tumors.
While it is now established that ADK of the ethmoid sinus originates in the olfactory cleft, very few studies have sought to assess the main sites prone to risk of recurrence after surgery [3][4]. Postoperative imaging fi ndings indicate that the olfactory cleft is rarely involved in recurrence, most likely due to its access during endoscopic surgery, whereas in our study the fovea ethmoidalis (47%; n=8/17), the posterior ethmoid (41%; n=7/17) and the lamina papyracea, essentially in its inferior part (41%; n=7/17) are sites of predilection for recurrence of ADK [ Figure 3].   To date, purely subjective outcomes have so far appeared encouraging but require greater long-term evaluation in a wider population, incorporating the same diffi culties as those highlighted above.
Chemotherapy, using 5-Fluorouracil, is applied topically on a nasal pack at the end of a complete surgical resection procedure as opposed to a suspicion of residual tumor. It remains in place for one week and is then renewed 2 or 3 times so as to eliminate any possible microscopic residue.
Knegt et al. [16] suggested this approach in a prospective study in 2001 in which he outlined signifi cant improvement in the overall 5 year survival rate in the group treated with topical chemotherapy after surgery (87% survival in the surgery plus topical chemotherapy group versus 39 to 59% in the surgery alone group).
In the same way, the progressive introduction of imagingguided surgery since the development of the late 1980s must theoretically contribute to the improvement of local control of cancer pathology by always allowing theoretically to facilitate complete removal of the tumor process. His interest appears real in advanced tumor stages where noble structures such as the orbit or the skull base are affected [17].
In our population, we used this aid for 25% of initial surgery cases and 22% of recurrence tumor cases. It is hard to say whether more frequent use of this tool had reduced our recurrence rates. In fact, Dalgorf et al., in a recent metaanalysis [18], were unable to demonstrate a statistically signifi cant benefi t for the use of imaging-guided surgery on the need for surgical revision (RR = 0.72) while this use is associated with a reduction in the rate of complications. It was also the same in the study of Ramakrishnan et al. [19]. Thus the recommendations [20] that have been published on the use of imaging-guided surgery are based on a low level of proof and the exact place of this tool remains to be defi ned according to the experience of the operators.

Conclusion
To our knowledge, this study is the fi rst of its kind to attempt an objective evaluation of MRI performance in early detection of recurrence or tumor residue in carcinoma of the ethmoid sinus and to identify the predominant sites prone to risk [7].
In our department we now recommend that this investigation should be performed systematically in the week after tumor resection, and followed by immediate surgical revision in the event of the slightest doubt. This investigation will then be repeated every 3 months This approach has yet to be approved in terms of patient survival benefi t.
Finally, certain areas seem particularly prone to risk of recurrence and should as such be subject to particular consideration during initial tumor resection.