Advanced Sinonasal Cancer Research Articles

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

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

Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 – 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. MethodsPatient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. ResultsThe different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. ConclusionThe results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

Radiotherapy Results in Locally Advanced Sinonasal Cancer: Turkish Society for Radiation Oncology, Head and Neck Study Group 01-005.

This study aims to examine the treatment outcomes and related factors in locally advanced sinonasal cancer across Turkiye. Twelve centers participants of the Turkish Society for Radiation Oncology Head and Neck Study Group attended the study. One hundred and ninety-four patients treated with intensity-modulated radiation therapy between 2001 and 2021 were analyzed retrospectively. The survival analysis was performed using the Kaplan-Meier method. Acute and late toxicity were recorded per Common Toxicity Criteria for Adverse Events V4.0. The median age was 58 years and 70% were male. The majority of tumors were located in maxillary sinus (59%). Most of the patients (%83) had T3 and T4A disease. Fifty-three percent of patients were in stage 4A. Radiotherapy was administered to 80% of the patients in the adjuvant settings. Median 66Gy dose was administered in median 31 fractions. Chemotherapy was administered concomitantly with radiotherapy in 45% of the patients mostly with weekly cisplatin. No grade ≥4 acute and late toxicity was observed. The median follow-up was 43 months. The 5-year and 10-year overall survival (OS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 61% and 47%; 69% and 61%; 72%, and 69%, and 56% and 49%, respectively. In the multivariate analysis, several factors demonstrated significant influence on OS, such as performance status, surgery, and lymph node involvement. Moreover, surgery was the key prognostic factor for LRFS. For DMFS, lymph node involvement and surgical margin were found to be influential factors. In addition, performance status and lymph node involvement were identified as significantly affecting PFS. In our study, the authors obtained promising results with IMRT. Performance status, lymph node involvement, and surgery emerged as the primary factors significantly influencing OS.

The SINTART 1 study. A phase II non-randomised controlled trial of induction chemotherapy, surgery, photon-, proton- and carbon ion-based radiotherapy integration in patients with locally advanced resectable sinonasal tumours

PurposeSinonasal tumours are rare diseases with poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment—induction chemotherapy (ICT), surgery and radiotherapy (RT)—modulated by histology and response to ICT. MethodsPatients with untreated, operable sinonasal tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enrolled in a single-arm, phase II, multicenter clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype, followed either by curative chemo-RT for pts with ≥80% reduction of initial tumour diameter or surgery and adjuvant (chemo)RT. Photon and/or proton/carbon ion-based RT was employed according to the disease site and stage. Primary end-point was 5-year progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate (ORR) per RECIST 1.1 and safety. ResultsThirty-five patients were evaluable for primary end-point. Fourteen patients (40%) were treated with definitive (CT)RT and 20 (57%) underwent surgery. Five-year PFS was 38% (95% confidence interval [CI], 21–69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28–75), with a median OS of 36 months. Three-year PFS—OS for pts achieving PR/CR versus stable disease (SD)/PD to ICT were 49.8–57% versus 43.2–53%, respectively. Three-year PFS for patients achieving major volumetric partial response (≥80% reduction of initial tumour volume, major partial volumetric response [mPRv]) versus non-mPRv were 82% versus 28% and 3-year OS were 92% versus 36% (p value 0.010 and 0.029, respectively). The ORR to ICT was 54% and 60% across all histotypes and in the sinonasal undifferentiated carcinoma (SNUC) subpopulation, respectively, with 6/15 SNUCs (40%) achieving mPRv. ConclusionTreatment of advanced sinonasal cancer with histology-driven ICT followed by (CT)RT in responsive patients was feasible. Overall, these findings suggest a possible role of ICT as the primary approach in newly diagnosed, resectable sinonasal tumours—especially SNUC—to select patients with favourable prognosis. Histology heterogeneity limits generalisation of trial results.

Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers.

Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.

A Patient Selection Approach Based on NTCP Models and DVH Parameters for Definitive Proton Therapy in Locally Advanced Sinonasal Cancer Patients.

Simple SummaryThe role of proton therapy as a radiation treatment option for locally advanced sinonasal cancer patients has increased in the last years, showing promising results in terms of clinical outcomes. Definition of strategies to identify patients who would benefit the most from proton therapy in terms of reduced toxicity is highly desirable, due to limited availability and higher costs of this treatment option. The novelty of our in silico study relies on assessing the suitability of a mixed dose volume histograms and normal tissue complication probability model-based approach, aiming at providing, to the scientific community, a patient selection criteria possibly leading the therapeutic choice between proton therapy and advanced photon techniques.(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the NTCP and DVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to NTCP > 3% for at least one severe toxicity, 4 (18.2%) due to NTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of NTCP and DVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing.

Including Surgical Resection in the Multimodal Management of Very Locally Advanced Sinonasal Cancer.

Sinonasal cancer often presents as locoregionally advanced disease. National guidelines recommend management of stage T4b tumors with systemic therapy and radiotherapy, but recent studies suggest that including surgical resection in the multimodal treatment of these tumors may improve local control and survival. We queried the National Cancer Database to examine patterns of care and outcomes in T4b sinonasal squamous cell carcinoma (SCC). Prospectively gathered data. National Cancer Database. Patients with T4b N0-3 M0 sinonasal squamous cell carcinoma diagnosed in 2004 to 2016 were stratified between those who received chemoradiotherapy and those who underwent surgical resection with neoadjuvant or adjuvant treatment. The overall survival of each cohort was assessed via Kaplan-Meier analysis and Cox proportional hazard models, with repeat analysis after reweighting of data via inverse probability of treatment weighting. Among 805 patients included in analysis, 2-year overall survival for patients undergoing surgical resection was 60.8% (95% CI, 56.1%-65.9%), while for patients undergoing chemoradiotherapy it was 46.7% (95% CI, 41.9%-52.0%). On Cox regression analysis, the inclusion of surgery in management was associated with improved survival in univariate analysis (hazard ratio [HR], 0.723 [95% CI, 0.606-0.862]; P < .001) and multivariate analysis (HR, 0.739 [95% CI, 0.618-0.885]; P = .001). Results with reweighted data were consistent in univariate analysis (HR, 0.765 [95% CI, 0.636-0.920]; P = .004]). Surgical treatment with neoadjuvant or adjuvant treatment for stage T4b sinonasal SCC was associated with promising survival outcomes, suggesting a role for incorporating surgery in treatment of select T4b SCC, particularly when removal of all macroscopic disease is feasible.

Karnofsky Performance Score - An Independent Prognostic Factor of Survival After Palliative Irradiation for Sino-nasal Cancer.

Sino-nasal cancer is rare and often diagnosed at advanced stages. Some patients cannot receive curative treatment and are treated with palliative irradiation. We aimed to identify prognostic factors for survival to facilitate treatment personalization for this group. Twelve patients treated with palliative radiotherapy for locally advanced sino-nasal cancer were retrospectively analyzed for survival. Ten characteristics were evaluated including age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin, tumor site, lymph node involvement, histology, equivalent dose in 2 Gy-fractions, completion of radiotherapy and concurrent chemotherapy. On univariate analysis, KPS ≥70 (p<0.001) and completion of radiotherapy (p<0.001) were significantly associated with better survival. Chemotherapy showed a trend (p=0.097). In the multivariate analysis, KPS ≥70 was significant (p=0.025), and completion of radiotherapy showed a trend (p=0.080). KPS is an independent predictor of survival for palliative irradiation of sino-nasal cancer. Patients require close monitoring and care for side effects, since completion of radiotherapy is important for survival.

Sinonasal cancers treatments: state of the art.

The present review provides the reader with the state-of-the-art concepts of sinonasal oncology in view of the latest literature data. Most recent publications in sinonasal oncology assessed treatment timing, centralization, surgical approach, margin status, orbit/neck management, salvage strategies, emerging surgical technologies, intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), particle radiotherapy, and neoadjuvant chemotherapy. Indications to endoscopic surgery for sinonasal cancer have plateaued and are unlikely to further expand. Endoscopic surgery provides noninferior results compared to open surgery and best suits timing constraints imposed by multimodal treatment. Management of orbit-encroaching sinonasal cancer is remarkably improving mostly owing to optimal use of nonsurgical strategies. Prognostic value of the margin status and management of the nodal basin and recurrent sinonasal tumors are far from being fully elucidated. Most promising surgical technologies are surgical navigation, optical imaging, and radiofrequency-aided ablation. IMRT and VMAT have theoretical technical advantages that are in the process of being clinically demonstrated. Pieces of evidence are progressively confirming the physical and radiobiological advantages offered by particle radiotherapy. Systemic therapy is being tested mostly in the neoadjuvant setting with the aim of improving outcomes in locally advanced sinonasal cancers; response to induction chemotherapy could better select a further locoregional approach.

Radical Exenteration of the Skull Base for End-Stage, Locally Advanced Sinonasal Malignancies: Challenging the Dictum of Unresectability

The role of surgery is not well defined in locally advanced sinonasal cancers with intracranial involvement after all medical options have been exhausted. We hypothesize that patients whose tumors are deemed unresectable and referred to palliative care may benefit from radical salvage surgery. We performed a single-center retrospective review of patients with malignant, locally advanced (stage T4b) sinonasal cancers with intracranial involvement from 2000 to 2020, inclusive. Data were collected on the patient demographics, details of chemotherapy, radiation, histology, perioperative complications, surgical approaches, and survival. We compared the survival outcomes of patients with different duration of disease before presentation. We identified 17 patients who had undergone salvage surgical resection of treatment-recalcitrant, locally advanced sinonasal tumors. Almost all patients had undergone prior surgery, radiotherapy, and chemotherapy. Perioperative complications occurred in 6 of 17 patients with 1 death. Patients with clinically less aggressive disease had significantly longer progression-free and overall survival compared with the more aggressive group. Salvage surgery for locally advanced sinonasal cancers with intracranial invasion that is recalcitrant to all other therapies should be considered for patients who otherwise have no other treatment options.

TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas.

Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy number losses were detected; overall, nearly all tumors (n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2, CCND1, MYC, FGFR1, and EGFR copy number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR, KRAS, and CDKN2A mutations, TERT copy number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer.

273P Long term outcomes of locally advanced &amp; borderline resectable esthesioneuroblastoma and sinonasal tumour with neuroendocrine differentiation treated with neoadjuvant chemotherapy

The present analysis was done to estimate the 5-year outcomes and late adverse events of locally advanced sinonasal tumours treated with induction chemotherapy followed by local therapy. Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumours treated between August 2010 to August 2014 with induction chemotherapy followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. COX regression analysis was used to identify factors impacting PFS and OS. The median follow-up was 5.15 years. The 5 year PFS in esthesioneuroblastoma cohort and in SNEC cohort was 63.5 %( 95%CI 28.9-84.7) and 34.6 % (95%CI 10.1-61.1) respectively (P=0.1). The only factor impacting PFS on multivariate analysis was a response to neoadjuvant chemotherapy (p=0.033). The 5 year OS in esthesioneuroblastoma cohort and in SNEC cohort were 91.7% (95%CI 53.9-98.9) and 46.2% (95%CI 19.2-69.6) respectively (p=0.024). Any grade late adverse event was seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Neoadjuvant chemotherapy in advanced sinonasal cancers is associated with improvement in 5-year outcomes. However, late side effects especially metabolic are seen in these patients and should be evaluated during follow up.

Trimodality Treatment of Very Locally Advanced Sinonasal Cancer: A National Cancer Database Analysis

Trimodality Treatment of Very Locally Advanced Sinonasal Cancer: A National Cancer Database Analysis

Long-term outcomes of locally advanced and borderline resectable esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation treated with neoadjuvant chemotherapy.

e18507 Background: Sinonasal tumors are a rare subgroup of head and neck cancers. Locally advanced esthesioneuroblastoma and sinonasal neuroendocrine tumors (SNEC) are treated with a multidisciplinary approach with combination of surgery followed by adjuvant radiation or chemo radiation; but have unsatisfactory outcomes. Hence we devised the approach of administering neoadjuvant chemotherapy (platinum and etoposide) followed by surgery and adjuvant chemoradiation. This approach had the advantage of improved response rates, orbital preservation and improvement in short term outcomes. The present analysis was done to estimate the 5 year outcomes and late adverse events of locally advanced sinonasal tumors treated with induction chemotherapy followed by local therapy. Methods: Twenty five patients with locally advanced esthesioneuroblastoma or SNEC treated between August 2010 to August 2014 with induction chemotherapy followed by local therapy were selected. The 5 year outcomes and late adverse events (CTCAE version 4.02) were noted. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. COX regression analysis was used to identify factors impacting PFS and OS. Results: The median follow up was 5.15 years. The 5 year PFS in esthesioneuroblastoma cohort and in SNEC cohort was 63.5% (95%CI 28.9-84.7) and 34.6% (95%CI 10.1-61.1) respectively (p = 0.1). The only factor impacting PFS on multivariate analysis was response to neoadjuvant chemotherapy (p = 0.033). The 5 year OS in esthesioneuroblastoma cohort and in SNEC cohort were 91.7% (95%CI 53.9-98.9) and 46.2% (95%CI 19.2-69.6) respectively (p = 0.024). Any grade late adverse event was seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Conclusions: Neoadjuvant chemotherapy in advanced sinonasal cancers is associated with improvement in 5 year outcomes. However late side effects especially metabolic are seen in these patients and should be evaluated during follow up. Keywords: Sinonasal; Adverse event; Esthesioneuroblastoma; SNEC; Induction; Neoadjuvant [Table: see text]

Outcomes of Locally Advanced Sinonasal Cancer in the Modern Era: Surgery and Adjuvant Therapy remains an Optimal Treatment Strategy

Outcomes of Locally Advanced Sinonasal Cancer in the Modern Era: Surgery and Adjuvant Therapy remains an Optimal Treatment Strategy

Primary Surgery for Locally Advanced Sinonasal Cancer: Influence of Dural and Orbital Resection

Primary Surgery for Locally Advanced Sinonasal Cancer: Influence of Dural and Orbital Resection

Long-term outcomes of locally advanced and borderline resectable esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation treated with neoadjuvant chemotherapy

Background: Sinonasal tumors are a rare group of neoplasms with limited data available regarding their treatment. Objectives: To estimate the 5 year outcomes and late adverse events of locally advanced sinonasal tumors treated with neoadjuvant therapy (NACT) followed by local therapy. Methods: Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumors treated between August 2010 and August 2014 with NACT followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. COX regression analysis was used to identify factors impacting PFS and OS. Results: The median follow-up was 5.15 years. The 5-year PFS in the esthesioneuroblastoma cohort and in the sinonasal neuroendocrine carcinoma (SNEC) cohort was 63.5% (95% confidence interval [CI]: 28.9–84.7) and 34.6% (95% CI: 10.1–61.1), respectively (P = 0.1). The only factor impacting PFS on multivariate analysis was a response to NACT (P = 0.033). The 5-year OS in the esthesioneuroblastoma cohort and in the SNEC cohort was 91.7% (95% CI: 53.9–98.9) and 46.2% (95% CI: 19.2–69.6), respectively (P = 0.024). Any grade late adverse events were seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Conclusion: NACT in advanced sinonasal cancers is associated with an improvement in 5-year outcomes. However, late side effects, especially metabolic, are seen in these patients and should be evaluated during follow-up.

The Evolving Role of Systemic Therapy in the Primary Treatment of Sinonasal Cancer.

The inclusion of systemic therapy in the multimodal approach of locally advanced sinonasal cancers, at least in some selected histologies, may improve locoregional control and reduce the frequency of distant metastasis, allowing longer survival. Response to induction chemotherapy is a strong prognostic factor for a patient's outcome and it may improve disease control by surgery and radiation. Concurrent chemoradiation aims at increasing locoregional control in squamous cell cancer of the head and neck; this is particularly important in sinonasal cancers, with a risk of local relapse of about 30%. Selected histologies may benefit from specific drug combinations, according to varying chemosensitivity. Intestinal-type adenocarcinoma carrying a functional p53 protein may be treated with preoperative cisplatin, 5-fluorouracil, and leucovorin. Sinonasal undifferentiated carcinoma is a chemosensitive disease, where the multimodal approach is necessary to counterbalance the severe prognosis. Sinonasal neuroendocrine carcinoma and olfactory neuroblastoma may benefit from systemic treatments, but their added value has not been so clearly defined yet. Multimodality trials are ongoing to test the activity of induction chemotherapy followed by locoregional curative treatment. A deeper knowledge of the molecular deregulations of these diseases could help in identifying targeted therapies.

Navigation-guided osteotomies improve margin delineation in tumors involving the sinonasal area: A preclinical study

ObjectivesTo demonstrate and quantify, in a preclinical setting, the benefit of three-dimensional (3D) navigation guidance for margin delineation during ablative open surgery for advanced sinonasal cancer. Materials and methodsSeven tumor models were created. 3D images were acquired with cone beam computed tomography, and 3D tumor segmentations were contoured. Eight surgeons with variable experience were recruited for the simulation of osteotomies. Three simulations were performed: 1) Unguided, 2) Guided using real-time tool tracking with 3D tumor segmentation (tumor-guided), and 3) Guided by 3D visualization of both the tumor and 1-cm margin segmentations (margin-guided). Analysis of cutting planes was performed and distance from the tumor surface was classified as follows: “intratumoral” when 0 mm or negative, “close” when greater than 0 mm and less than or equal to 5 mm, “adequate” when greater than 5 mm and less than or equal to 15 mm, and “excessive” over 15 mm. The three techniques (unguided, tumor-guided, margin-guided) were statistically compared. ResultsThe use of 3D navigation for margin delineation significantly improved control of margins: unguided cuts had 18.1% intratumoral cuts compared to 0% intratumoral cuts with 3D navigation (p < 0.0001). ConclusionThis preclinical study has demonstrated the significant benefit of navigation-guided osteotomies for sinonasal tumors. Translation into the clinical setting – with rigorous assessment of oncological outcomes – would be the proposed next step.

1102P - Sinonasal non-glandular cancers relapsing after multimodal treatments

Background: Multimodality treatment (MMT) is the current approach to advanced sinonasal cancers (SC). We lack salvage treatment standardization especially for pts already receiving MMT. No clinical factors able to predict outcome have been identified in this disease setting. Methods: We retrospectively analyzed a series of pts with recurrent/metastatic (RM) SC after multimodal curative treatment, consisting in induction chemotherapy (iCT) followed by locoregional therapy. Overall survival (OS) was measured as the interval from relapse to death. Results: Among 106 pts with SC treated with MMT at our Center from 1997 to 2016, 50 (M/F 31/19) relapsed. Median age was 53 yrs (16-73). Median follow-up was 26 months (m) (5-192). WHO 2005 histotypes were: 36% sinonasal undifferentiated carcinoma (SNUC), 34% squamous cell cancer (SCC), 30% carcinomas with neuroendocrine differentiation (CND). Median time to first relapse after curative treatment was 13.5 m. Median OS was 13 m from recurrence: 19 m in SCC, 16 m in SNUC and 6 m in CND (p = .34). Relapse occurred as distant metastasis in 40%, as nodal recurrence in 6% and at primary site in 54% of cases. First line salvage treatment was surgery in 38% (14 pts received surgery on T, 2 on N and 3 on M), CT in 30%, RT in 8%, best supportive care in the remaining pts. Median OS was 31 m in surgically treated pts and 4.8 m in those receiving CT (p < .0001). In pts with disease control (PR+SD) after iCT, median OS after recurrence was longer than in pts with PD (13.4 vs 1.5 m, p = .07). Median OS from relapse was 29.6 m in pts with CR after definitive treatment, 7.1 m in those with PR and 3.4 m in those with PD (p = .002). Pts with an objective response to palliative CT had a longer median OS than those with PD (20 vs 4 m, p = .002). Conclusions: Prognosis of SC relapsing after MMT is dismal. With the caveat of a retrospective analysis and a case series that has been collected in a long time frame, we showed that feasibility of salvage surgery, objective response to prior definitive treatment and response to palliative CT are factors associated with better outcomes. Pts with relapsed or metastatic SC not amenable to salvage surgery should be considered for enrolment in clinical trials. Legal entity responsible for the study: Fondazione IRCCS Istituto Nazionale Tumori Milano - Università degli Studi di Milano. Italy Funding: None Disclosure: All authors have declared no conflicts of interest.