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

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 cranio-endoscopic 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. (c) 2020 S. Karger AG, Base

Critical review of multidisciplinary approaches for managing sinonasal tumors with orbital involvement

Orbital invasion is frequently observed in tumors involving the maxillary, ethmoid and frontal sinuses given the proximity of the orbit to the sinonasal tract and ventral skull base. The main objective of the present review is to determine the existing evidences on the frequency, treatment, and outcomes of orbital invasion in benign and malignant sinonasal tumors. A systematic review of the literature published from 1995 to 2020 was performed and data sources included PubMed, Cochrane library, NCBI Bookshelf, National Guideline Clearinghouse. Orbital invasion was reported in 2-4% of inverted papillomas, 12-15% of fibro-osseous lesions, 27-32% of juvenile angiofibromas, 35-45% of low-grade malignancies, and 50-80% of high-grade cancers. Surgical resection with negative margins represents the cornerstone of management for benign and low-grade malignant tumors. Histology-specific induction chemotherapy can be used for high-grade sinonasal cancers in order to downstage the tumor and increase the possibility of orbital preservation. When a significant response to induction chemotherapy is observed, exclusive chemoradiation should be offered to improve overall survival rates. Appropriate reconstruction of any surgical defects is essential in order to minimize complications and optimize functional and aesthetic outcomes. Orbital apex invasion represents a negative prognostic factor. In conclusion, a multidisciplinary teamwork is mandatory to maximize local control, minimize morbidity and improve orbital preservation rates

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

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% \ub1 7.45% and 61.9% \ub1 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, 2020

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\u201335, 2022

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%\u2009\ub1\u20096.5% versus 57.6%\u2009\ub1\u200915.4%, P\u2009=\u20090.03) and RFS (92.3%\u2009\ub1\u20097.39% versus 80.2%\u2009\ub1\u20098.88%, P\u2009=\u20090.05). Using multivariate analysis, OS was independently determined by poRT (Hazard Ratio\u2009=\u20090.16; P\u2009=\u20090.03) 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

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 ther-apeutic 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 imple-mented 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