Intraoperative surgical navigation as a precision medicine tool in sinonasal and craniofacial oncologic surgery.

INTRODUCTION: Recent evidence supports the efficacy of surgical navigation (SN) in improving outcomes of sinonasal and craniofacial oncologic surgery. This study aims to demonstrate the utility of SN as a tool for integrating surgical, radiologic, and pathologic information. Additionally, a system for recording and mapping biopsy samples has been devised to facilitate sharing of spatial information. MATERIALS AND METHODS: SN was utilized for biopsy mapping in 10 sinonasal/craniofacial oncologic procedures. Twenty-five raters with experience in anterior skull base oncology were interviewed to identify 15 anatomical structures in preoperative imaging, relying on topographical descriptions and surgical video clips. The difference in the localization of anatomical structures by raters was analyzed, using the SN-mapped coordinates as a reference (this difference was defined as spatial error). RESULTS: The analysis revealed an average spatial error of 9.0 mm (95 % confidence interval: 8.3-9.6 mm), with significant differences between surgeons and radiation oncologists (7.9 mm vs 12.5 mm, respectively, p < 0.0001). The proposed model for transferring SN-mapped coordinates can serve as a tool for consultation in multidisciplinary discussions and radiotherapy planning. CONCLUSIONS: The current standard method to evaluate disease extension and margin status is associated with a spatial error approaching 1 cm, which could affect treatment precision and outcomes. The study emphasizes the potential of SN in increasing spatial precision and information sharing. Further research is needed to incorporate this method into a multidisciplinary workflow and measure its impact on outcomes.

Surgical management of advanced sinonasal cancer: a 10-year mono-institutional experience.

Objective: Endoscopic endonasal surgery is effective in the treatment of sinonasal cancers. However, in cases of well-differentiated locally advanced neoplasms as well as recurrences, the most appropriate treatment is debated. The purpose of this study is to report a mono-institutional experience on craniofacial surgery performed in a tertiary-care referral centre. Methods: This was a retrospective analysis of 90 patients treated with transcranial and/or transfacial resection for sinonasal cancer between 2010 and 2020. Outcome measures included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and recurrence-free survival (RFS). Results: The 5-year OS, DSS and DFS were 48.2%, 60.6% and 28.7%, respectively. Factors correlated with prognosis were pT-classification (p = 0.002), histotype (p = 0.012) and dural involvement (p = 0.004). Independent prognostic factors were orbital apex infiltration (p = 0.03), age (p = 0.002) and adjuvant therapy (p = 0.03). Conclusions: When endoscopic endonasal surgery is contraindicated and chemoradiotherapy is not appropriate, craniofacial and transfacial approaches still represent an option to consider, despite the non-negligible morbidity.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. METHODS: Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. RESULTS: The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. CONCLUSION: NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Squamous Cell Carcinoma of the Nasal Vestibule: A Multi-Centric Observational Cohort Study.

OBJECTIVES: Squamous cell carcinoma of the nasal vestibule (NV-SCC) is a rare but challenging entity, due to the complex anatomy of the region. Consensus on the best treatment strategy is still lacking, as well as a dedicated staging system. Our aim was to analyze oncological outcomes of surgically treated patients and to investigate possible prognostic factors. METHODS: We performed a retrospective multi-centric observational study including six Academic Hospitals over a 10-year period, including only patients who underwent upfront surgery for primary NV-SCC. Patients were staged according to all currently available staging systems. The Kaplan-Meier method was used to compute overall, disease-free, and disease-specific survival. Logistic regression models were used to correlate between survival outcomes and clinical and pathological variables. RESULTS: Seventy-one patients with a median follow-up of 38 months were included in the study. Partial and total rhinectomy were the most commonly performed procedures, respectively, in 49.3% and 25.4% of cases. Neck dissection was performed on 31% of patients, and 45.1% of them underwent adjuvant radiotherapy. Three years overall, disease-specific and disease-free survival were, respectively, 86.5%, 90.3%, and 74.2%. None of the currently available staging systems were able to effectively stratify survival outcomes. Factors predicting lower overall survival on multivariate analysis were age (p = 0.021) and perineural invasion (p = 0.059), whereas disease-free survival was negatively affected by age (p = 0.033) and lymphovascular invasion (p = 0.019). CONCLUSION: Currently available staging systems cannot stratify prognosis for patients who underwent surgery for NV-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2634-2645, 2024.

Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram.

Introduction: The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Methods: Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. Results: A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Conclusion: Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.

Patterns of recurrences in sinonasal cancers undergoing an endoscopic surgery-based treatment: Results of the MUSES* on 940 patients: *MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

OBJECTIVES: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. MATERIALS AND METHODS: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. RESULTS: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. CONCLUSION: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

Maxillary Sinus Floor Infiltration: Results From a Series of 118 Maxillary Sinus Cancers.

OBJECTIVES/HYPOTHESIS: Maxillary cancers are rare and aggressive tumors, which can spread beyond the sinus bony walls. Preoperative assessment of infiltration of maxillary sinus floor (MSF) is paramount for surgical planning, as palatomaxillary demolition significantly impacts patients' quality of life. This study investigates the challenges involved in the preoperative and intraoperative evaluation of MSF infiltration and analyzes its prognostic relevance. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of patients treated for sinonasal malignancies at a single Institution was performed. Patients receiving surgical-based treatment with curative intent for primary maxillary sinus cancers, between January 2000 and November 2019, were included. RESULTS: A cohort of 118 patients was analyzed. By comparing intraoperative findings (endoscopic assessment and frozen sections) with preoperative radiological assessment, diagnostic changes with regard to MSF infiltration were found in 27.1% (32/118 cases). MSF infiltration negatively affected the prognosis in both univariate and multivariate analyses in the overall population. In the subgroup of pT1-T3 tumors, MSF infiltration was significantly associated with reduced overall (P = .012), disease-free (P = .011), and distant recurrence-free (P = .002) survival rates. Conversely, pT classification was not able to stratify patients according to prognosis, mainly because early-staged cancers (pT1-T2) with MSF infiltration showed reduced survival rates, similar to those observed in pT3 cancers. CONCLUSIONS: Preoperative imaging should be integrated with intraoperative findings based on endoscopic inspection and frozen sections. Future studies are required to investigate the opportunity to incorporate MSF infiltration in the TNM staging system, considering its crucial role in defining the extent of surgery and its potential as prognosticator. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:26-35, 2022.

Methylation Drivers and Prognostic Implications in Sinonasal Poorly Differentiated Carcinomas.

BACKGROUND: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose. METHODS: Histopathological review and immunohistochemical study was performed on 53 PDSNCs. Molecular analysis included mutational profile by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile using LINE-1 bisulfite-PCR and pyrosequencing analysis. RESULTS: Nine SWI/SNF complex defective cases and five IDH2 p.Arg172x cases were identified. A significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation was observed (p = 0.002 and p = 0.032, respectively), which were associated with a worse prognosis (p = 0.007). CONCLUSIONS: Genetic and epigenetic characterization of PDSNCs should be performed to identify distinct prognostic entities, which deserved a tailored clinical treatment.

Squamous Cell Carcinoma of Nasal Vestibule and Pyramid: Outcomes and Reconstructive Strategies.

OBJECTIVES: Squamous cell carcinoma of nasal vestibule and pyramid is rare, thus classification, treatment protocol, and indications for elective neck treatment are still controversial. Nasal reconstruction is challenging, as well, and prosthesis is still used. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of patients surgically treated from 2010 to 2018 in a single Institution. Advanced tumors were further treated with adjuvant irradiation. Reconstruction strategy included grafts, locoregional and free flaps, and was customized on layers removed. RESULTS: Forty-five patients were enrolled. The 5-year overall survival and disease-free survival were 81.9% ± 7.45% and 61.9% ± 9.09%, respectively. Wang's classification, site of origin, extent of surgery and margins status significantly correlated with prognosis and recurrence rate. Regional recurrences occurred in patients affected by advanced tumors who did not receive any form of elective neck treatment. CONCLUSION: Multidisciplinary management and a proper reconstructive algorithm are recommended. Adjuvant irradiation and elective neck treatment should be advocated for advanced stage high-risk patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E1198-E1208, 2021.

Transnasal Endoscopic Surgery: Surgical Techniques and Complications.

Nowadays, surgeons have a wide armamentarium of surgical approaches available to safely treat sinonasal malignancies, which includes open approaches, with the traditional craniofacial resection (CFR), and endoscopic transnasal techniques. The correct choice depends on the features of the pathology. It is well known that endoscopic approaches have a lower morbidity compared with traditional open techniques, due to a shorter hospitalization, absence of facial incisions, and avoidance of brain retraction. Moreover, endoscopic surgery presents clear technical advantages. For example, magnification of the surgical field allows the surgeon to carefully identify tumor margins, the site of origin, and the anatomical structures involved by the lesion. Nevertheless, a purely endoscopic approach cannot always provide successful resection of the tumor; the patient must be informed about the possibility of switching to a combined cranioendoscopic resection or CRF, depending on the effective extension of the disease evaluated intraoperatively. Despite these advantages, postoperative complications can occur after endoscopic endonasal surgery, as in any surgical intervention; however, complications after these procedures are less severe and less frequent compared with traditional open approaches. The most common complications observed include skull base reconstruction failure, intraoperative vascular lesions, and orbital or central nervous system complications. Thus, endoscopic endonasal resection, when properly planned and performed by experienced surgeons, is an acceptable treatment for well-selected skull base malignancies with long-term outcomes comparable to those achieved with traditional external approaches.

Multidisciplinary treatment algorithm for the management of sinonasal cancers with orbital invasion: A retrospective study.

BACKGROUND: Sinonasal cancers frequently involve the orbit with resulting controversies on whether to remove or preserve the orbital contents. METHODS: Retrospective review of patients with primary sinonasal cancer involving the orbit, treated according to a multidisciplinary protocol tailored to tumor histology and extent of orbital invasion in two tertiary care referral centers over a 20-year period. RESULTS: The oncological and functional outcomes of 163 patients were analyzed. The degree of orbital involvement significantly affected both overall (P < .0001) and disease-free (P < .0001) survival. Orbital apex invasion was an independent negative prognostic factor (5-year overall survival, 14.6% ± 7.5%), with dismal prognosis regardless of the treatment adopted. An appropriate use of induction chemotherapy and endoscopic-assisted surgery allowed for orbital preservation in 76.6% of cases; 96% of patients treated using an orbit-sparing approach maintained a functional eye after treatment. CONCLUSION: The multimodal treatment algorithm herein proposed was able to maximize orbital preservation rates with acceptable oncological and functional outcomes.

Sinonasal Non-Intestinal-Type Adenocarcinoma: A Retrospective Review of 22 Patients.

OBJECTIVE: To analyze outcomes and prognostic factors of sinonasal nonsalivary non-intestinal-type adenocarcinoma (n-ITAC.) METHODS: A retrospective review of 22 consecutive patients with n-ITAC was performed. RESULTS: Average follow-up time was 77 months. The 5-year overall survival and disease-specific survival were 95.2%. The 5-year overall survival and disease-specific survival were 100% for pT1, pT2, and pT3 tumors and 83.3% for pT4a and pT4b tumors; 100% for G1 tumors and 87.5% for G3 tumors; and 100% for tumors with negative surgical margin and 50% for tumors with positive surgical margin. Stage, grade, and surgical margins were independent prognostic factors. Adjuvant radiotherapy was performed for high-grade and high-stage tumors. CONCLUSIONS: Surgery followed by radiotherapy has remained a mainstay for management of n-ITAC, and the endoscopic transnasal approach, when correctly planned and indicated, is the surgery of choice. Adjuvant radiotherapy is recommended in cases of high-stage (T3 and T4) and high-grade tumors. n-ITAC is associated with a favorable outcome. High grade, pT4 stage, and positive surgical margins are independent negative prognostic factors.

Endoscopic Endonasal Reconstruction of Anterior Skull Base Defects: What Factors Really Affect the Outcomes?

OBJECTIVE: Endoscopic endonasal surgery has evolved in recent decades, requiring comparable advances in reconstructive techniques. This study aimed to retrospectively review outcomes of endoscopic anterior skull base reconstruction and to analyze factors associated with failures. METHODS: Data from patients who underwent endoscopic endonasal anterior skull base reconstruction in a single institution between 1998 and 2017 were collected. Patients were stratified according to selected risk factors: sex; age; previous surgery; disease treated (cerebrospinal fluid leaks, benign tumors, malignant tumors); single or multiple defects; defect dimension (<1 cm2, 1-2 cm2, 2-6 cm2, >6 cm2) and site (olfactory cleft, ethmoidal roof, planum sphenoidalis, posterior wall of frontal sinus); reconstruction technique (overlay graft, multilayer grafts, pedicled flap) and materials used; postoperative radiotherapy; and year of surgery. Statistical significance was assessed using Fisher exact test. Univariate logistic regression was implemented to analyze the association between risk factors and failures. RESULTS: Inclusion criteria were met by 513 cases with median follow-up of 96 months (range, 12-257 months). Success rate for initial repair was 95% (487/513), with 100% success rate for secondary closure after revision surgery. Failures were not significantly related to sex (P = 0.54), reconstruction technique (P = 0.28), location of defect (P = 0.65), dimension (P = 0.69), disease (P = 0.83), or postoperative radiotherapy (P = 0.83). Year of surgery, considered as a continuous variable, was associated with a statistically significant reduction of failures (odds ratio = 0.89, P = 0.005). CONCLUSIONS: Endoscopic surgery is safe and effective for anterior skull base reconstruction. Refinements in surgical technique and increasing experience have contributed to improved success rates.

Endoscopic endonasal approach for sinonasal and anterior skull base malignancies in the elderly.

BACKGROUND: The purpose of this study was to report the outcomes of endoscopic transnasal resection for sinonasal and anterior skull-base cancers in elderly patients. METHODS: A retrospective review was performed. The patients were divided into 2 groups, <70 years old and ≥70 years old and compared by univariate analysis. Prognostic factors were evaluated with a multivariate analysis. Survival rates were also calculated. RESULTS: Two hundred three elderly patients and 397 younger patients were enrolled in this study. The elderly patients reported lower survival rates than the younger patients. When melanoma and esthesioneuroblastoma were censored, the disease-specific survival (DSS) and recurrence-free survival (RFS) were similar. Complication rates were 17.5% without any statistical significance between the groups. Multivariate analysis revealed that histology, stage, surgical margins, and surgical approaches were independent predictors of survival in elderly patients. CONCLUSION: The endoscopic transnasal approach reported low mortality and morbidity rates also in geriatric patients, and age itself is not to be considered as a contraindication.

Complications and donor site morbidity of 3-layer reconstruction with iliotibial tract of the anterior skull base: Retrospective analysis of 186 patients.

BACKGROUND: Anterior skull base reconstruction after resection of sinonasal cancers may be challenging when pedicled flaps are unavailable. The purpose of the present study was to analyze the complication rate and donor site morbidity of 3-layer reconstruction with the iliotibial tract (ITT). METHODS: We retrospectively reviewed all anterior skull base reconstructions with ITT performed from 2007 to 2015. Donor site morbidity was investigated by a dedicated questionnaire. Factors impacting on cerebrospinal fluid (CSF) leak were assessed using the Fisher's exact test. RESULTS: One hundred eighty-six patients were included. The overall complication rate was 9.7%. A CSF leak occurred in 11 patients (5.8%). Twenty patients (10.8%) and 130 patients (69.9%) underwent previous or adjuvant radiotherapy, respectively. Neither radio(chemo)therapy nor age impacted the risk of CSF leak. Six patients (3.2%) experienced complications at the donor site. The questionnaire demonstrated minimal functional and aesthetic morbidity. CONCLUSION: Three-layer reconstruction with the ITT is a safe procedure with acceptable complication rate and donor site morbidity.

Prognostic value of pretreatment peripheral blood markers in paranasal sinus cancer: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

BACKGROUND: Pretreatment hematological markers have emerged as prognostic factors for several cancers. The purpose of this study was to present our investigation of the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting recurrence and mortality for patients with primary sinonasal cancers (SNCs). METHODS: We carried out a retrospective review of patients with SNC who had been treated using endoscopic approaches from 2002 to 2014 at a single institute. The endpoints analyzed were overall survival (OS) and disease-free survival (DFS). RESULTS: Of 365 patients treated, 215 fulfilled the inclusion criteria. Analysis of epithelial tumors (adenocarcinoma and carcinoma) and advanced-stage cancers (pT3-T4) showed shorter OS and DFS in those patients with higher NLR and PLR. Furthermore, the NLR and PLR were revealed as independent prognostic factors for DFS, with a reduced risk of recurrence in patients with NLR <2.6 (hazard ratio [HR], 0.39; p = .02) and PLR <156.9 (HR, 0.34; p = .001). CONCLUSION: High pretreatment NLR and PLR are associated with poor prognosis in patients affected by epithelial advanced-stage SNC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 730-736, 2017.

Treatment strategies for primary early-stage sinonasal adenocarcinoma: A retrospective bi-institutional case-control study.

OBJECTIVE: To investigate different treatment strategies for primary early-stage (pT1-T2) sinonasal adenocarcinomas. METHODS: Retrospective case-control study. From 2000 to 2011, 61 cases were radically resected using an endoscopic endonasal approach. Surgery as a single treatment modality was adopted for 33 patients (study group) while it was followed by postoperative radiotherapy (poRT) in 28 patients (control group). RESULTS: Median follow-up was 61 and 67 months for the study and control group respectively. Patients were stratified according to the pT classification and no statistically significant differences were found in terms of Overall (OS) and Recurrence-free (RFS) survival. When analyzing the high-grade tumors (47 cases), statistically significant differences were observed between the control and study groups both in terms of OS (90.5% ± 6.5% versus 57.6% ± 15.4%, P = 0.03) and RFS (92.3% ± 7.39% versus 80.2% ± 8.88%, P = 0.05). Using multivariate analysis, OS was independently determined by poRT (Hazard Ratio = 0.16; P = 0.03) thus confirming its protective role for high-grade adenocarcinomas. CONCLUSION: Our preliminary results suggest that endoscopic endonasal surgery could be used as a single treatment modality for primary early-stage low-grade sinonasal adenocarcinoma, resected with negative margins. Surgery followed by poRT offers the best treatment strategy not only for advanced-stage lesions but also for high-grade adenocarcinomas, regardless of the stage of disease at presentation.