Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review.

BACKGROUND: The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. CASE: Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation. CONCLUSION: This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

Durable and dramatic response to checkpoint inhibition combined with COX-2 inhibitor celecoxib in a patient with p16+ metastatic sinonasal undifferentiated carcinoma: A case study.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease. CASE: A 56-year-old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX-2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune-related adverse events successfully treated with steroids. CONCLUSION: Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Sinonasal NUT carcinoma: A consecutive case series and systematic review.

BACKGROUND: Sinonasal NUT carcinoma is an extremely rare, lethal malignancy with limited literature. METHODS: A case series was conduction of all patients with sinonasal NUT carcinoma at a single institution between 2010 and 2022. Survival and associated were evaluated. A systematic review of the literature was performed. RESULTS: In 12 patients, followed for a median of 1.5 years, the median overall survival (OS) and disease-specific survival (DSS) were both 14.6 months. Patients with maxillary sinus tumors were 91% more likely to survive (hazard ratio [HR]: 0.094, 95% confidence interval [CI]: 0.011-0.78, p = 0.011). Patients with higher-stage disease stage had worse OS (stage IVb-c vs. III-IVa, p = 0.05). All three patients who were alive with no evidence of disease received induction chemotherapy. CONCLUSION: For patients with sinonasal NUT carcinoma, the median survival was 15 months but better with lower-stage and maxillary tumors. Induction chemotherapy may be beneficial.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Impact of Clinical Factors and Treatments on SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma.

The objective of this study was to report outcomes for 19 consecutive patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma. Patients were treated from 2014 to 2021 and followed for a median of 22.3 months. The median overall survival (OS) and disease-free survival (DFS) were 31.8 and 9.9 months, respectively. Patients with nasal cavity or maxillary sinus tumors had 84% better disease-specific survival (DSS) (hazard ratio [HR], 0.136; 95% confidence interval [CI], 0.028-0.66; p = .005) and 71% better DFS (HR, 0.29; 95% CI, 0.097-0.84; p = .041) than patients with other sinonasal sites. Patients who received induction chemotherapy were 76% less likely to die of disease (DSS HR, 0.241; 95% CI, 0.058-1.00; p = .047). In the largest single-institution study of SMARCB1-deficient sinonasal carcinoma to date, OS and DFS approached 3 years and 1 year, respectively, but were better for nasal cavity and maxillary sinus tumors. Patients may benefit from induction chemotherapy.

The Role of Induction Therapy for Sinonasal Cancers.

OPINION STATEMENT: The role of induction chemotherapy in sinonasal cancers is promising; however, prospective studies with higher grades of evidence are needed. With the currently available literature, the authors would advocate for the use of induction chemotherapy (IC) in locally advanced sinonasal squamous cell carcinoma (T3-T4) for organ preservation and potentially for improved survival outcomes. In sinonasal undifferentiated carcinoma (SNUC), IC should be considered in all patients given its tendency for aggressive invasion and poor outcomes. In SNUC, response to IC may direct the modality of definitive treatment to follow. In responders (partial or complete), chemoradiation therapy should be strongly considered. In non-responders or in those with progression of disease, surgical therapy is favored. For esthesioneuroblastoma, surgical resection with negative margins and adjuvant radiation therapy remains the gold standard. However, IC may be considered for locally advanced disease especially with orbital invasion or in recurrent/distant disease. There is no definite indication for IC in sinonasal adenoid cystic carcinoma or sinonasal adenocarcinoma. Recommendations are summarized in Table 1.

Definitive-intent (chemo)radiotherapy for sinonasal undifferentiated carcinoma.

OBJECTIVE: The current study aimed to investigate the value of definitive-intent (chemo)radiotherapy in treating sinonasal undifferentiated carcinoma (SNUC) in a single institution. METHODS: The medical records of 21 patients with SNUC treated with definitive-intent (chemo)radiotherapy between 2011 and 2021 in one single institution were retrospectively reviewed. We analyzed the treatment efficiency and long-term survivals. RESULTS: A total of 21 patients were included in this cohort, 12 patients presented with T4 stage at diagnosis, and 6 in T1/T2, 3 in T3 stage. Nine patients (42.9%, 9/21) showed cervical lymph node metastases. All the patients were scheduled to receive definitive (chemo)radiotherapy and five patients had been performed surgery for residual tumor after (chemo)radiotherapy. 66.7% (14/21) of patients had a complete response after the completion of treatment, 23.8% (5/21) of partial response, one of stable disease, and one of progressed disease. The 3-year overall survival of the entire group were 86.2%, and the 3-year progress-free survival were 66.3%, respectively. 52.4% of the patients (11/21) presented orbit invasion, compared with patients without orbit invasion, the patients who had orbit invasion were not found to have significantly poor 3-year overall survival (87.5% vs 83.3%, p = 0.38) and 3-year progression-free survival (75.0% vs 55.3%, p = 0.59). CONCLUSION: Definitive-intent (chemo)radiotherapy could be the preferred treatment for patients with advanced SNUC, and salvage surgery should be performed for the lesions showing stable disease, progressed disease, or residual tumor. ADVANCES IN KNOWLEDGE: The value of definitive chemoradiotherapy in treating sinonasal undifferentiated carcinoma.

Intracranially Extended Sinonasal Undifferentiated Carcinoma: A Case Report and Literature Review.

BACKGROUND Sinonasal undifferentiated carcinomas (SNUC) are highly malignant and rare lesions. Therapeutic efforts often provide frustrating results. Their course is characterized by indolent progression, until it culminates in extensive local infiltration of adjacent anatomical structures or cervical lymphadenopathy in approximately one-third of patients upon admission. It most frequently affects males, with a sex ratio of 3: 1. The age at manifestation tends to be about 40-50 years. CASE REPORT We report the case of a 41-year-old man with intracranial expansion of SNUC. Two previous sinus surgeries were performed endoscopically because the lesion at that moment was exclusively located endonasally. Within the last few months, he had been having persistent headaches. Magnetic resonance imaging (MRI) revealed an anterior cranial fossa lesion. Therefore, he underwent a bifrontal craniotomy and excision of the space-occupying lesion (SOL). The osseous defect of the skull base was covered with a titanium mesh. Finally, we performed a duraplasty using a pericranial flap and fat tissue taken from his abdomen. Postoperatively, his wound was dehisced. We proceeded then to a frontal craniectomy with surgical debridement, subgaleal empyem and epidural abscess removal, and copious irrigation with oxygen peroxide. Enterococcus spp. were isolated from pus cultures. Despite receiving bacteria-focused antibiotics, he unfortunately developed sepsis and died. The histopathologic findings revealed a SNUC, which is the criterion standard for diagnosis. CONCLUSIONS Multimodal treatment offers the best prognosis to patients with SNUC. Combined operations by otolaryngologists and neurosurgeons provide the necessary radicality. There is high risk of wound healing disorders, especially when local irradiation had been administered.

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.

Salvage surgery improves the treatment outcome of patients with residual/recurrent maxillary sinus cancer after superselective intra-arterial cisplatin infusion with concomitant radiation therapy.

PURPOSE: We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. METHODS: We assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. RESULTS: Twenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period. Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. CONCLUSION: Treatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.

Management of sinonasal cancers: Survey of UK practice and literature overview.

INTRODUCTION: Sinonasal malignancy is a rare and heterogenous disease, with limited evidence to guide management. This report summarises the findings of a UK survey and expert workshop discussion which took place to inform design of a proposed UK trial to assess proton beam therapy versus intensity-modulated radiation therapy. METHOD: A multidisciplinary working group constructed an online survey to assess current approaches within the UK to surgical and non-surgical practice. Head and neck clinical oncologists, ear nose and throat (ENT) and oral-maxillofacial (OMF) surgeons were invited to participate in the 42-question survey in September 2020. The Royal College of Radiologists Consensus model was adopted in establishing categories to indicate strength of response. An expert panel conducted a virtual workshop in November 2020 to discuss areas of disagreement. RESULTS: A survey was sent to 140 UK-based clinicians with 63 responses (45% response rate) from 30 centres, representing a broad geographical spread. Participants comprised 35 clinical oncologists (56%) and 29 surgeons (44%; 20 ENT and 9 OMF surgeons). There were variations in preferred sequence and combination of treatment modalities for locally advanced maxillary squamous cell carcinoma and sinonasal undifferentiated carcinoma. There was discordant surgical management of the orbit, dura, and neck. There was lack of consensus for radiotherapy in post-operative dose fractionation, target volume delineation, use of multiple dose levels and treatment planning approach to organs-at-risk. CONCLUSION: There was wide variation across UK centres in the management of sinonasal carcinomas. There is need to standardise UK practice and develop an evidence base for treatment.

Imaging predictor of ophthalmic involvement in maxillary sinus cancer during super selective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT).

OBJECTIVE: To investigate the predictability of ophthalmic artery involvement in maxillary sinus cancer using preprocedural contrast enhanced CT and MRI. METHODS: We analyzed advanced (T3, T4a, and T4b) primary maxillary sinus squamous cell carcinoma treated with super-selective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) from Oct 2016 to Mar 2020. Two diagnostic radiologists evaluated the tumor invasion site around the maxillary sinus using preprocedural imaging. These results were compared with the angiographic involvement of the ophthalmic artery using statistical analyses. We also evaluated our RADPLAT quality using complication rate, response to treatment, local progressive free survival (LPFS), and overall survival (OS). RESULTS: Twenty patients were included in this study. There were ten cases of ophthalmic artery tumor stain and there was a correlation between ophthalmic artery involvement and invasion for ethmoid sinus with statistically significant differences. Other imaging findings were not associated with ophthalmic artery involvement. CONCLUSIONS: Ethmoid sinus invasion on preprocedural imaging could suggest ophthalmic artery involvement in maxillary sinus cancer. It may be useful in predicting prognosis and treatment selection.

Complete response to immunotherapy in sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon aggressive tumor. Locally advanced disease is usually diagnosed at presentation. Multidisciplinary approach is essential and aims to ensure optimal trimodal strategy. Induction chemotherapy is preferred in order to select patients who will benefit from chemoradiotherapy or surgery. Immunotherapy is not indicated in patients with recurrent SNUC. We describe an impressive response in a young man previously treated with radiotherapy and chemotherapy and demolitive surgery who had metastatic bone and lung disease. We also report data on PD-L1, next-generation sequencing, and neutrophil/platelets ratio.

Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene.

BACKGROUND: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. METHODS: We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. RESULTS: Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. CONCLUSION: Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

[Therapeutic management and prognostic profile of a patient with maxillary sarcomatoid carcinoma (case report)]. / Carcinome sarcomatoïde: prise en charge thérapeutique et profil pronostique à propos d´une localisation maxillaire inhabituelle (à propos d´un cas).

Sarcomatoid carcinoma is a rare, aggressive, malignant tumor with a poor prognosis and a very high frequency of recurrence. Carcinoma of the maxillary sinus is extremely rare. We report the case of a 42-year-old woman with left maxillary process. Biopsy revealed aggressive sarcomatoid carcinoma with a lymph-node metastasis. The patient underwent surgical excision, lymph-node dissection followed by radiotherapy with good outcome. The rarity of this site-specific cancer poses a problem of diagnosis and timely management which is still a controversial topic. However, wide surgical excision is the gold standard treatment. This study highlights the anatomoclinical peculiarities and, in particular, the prognostic features of this tumor.

Targeting MET Amplification with Crizotinib in a Case of Sinonasal Undifferentiated Carcinoma.

Comprehensive molecular testing of individual tumors has led to the identification of novel molecularly defined cancer therapies and treatment indications. Given low frequencies of many molecular alterations, efficacy of therapies used to target them are often undefined, especially in the context of rare malignancies. Here we describe the first reported case of MET amplification in sinonasal undifferentiated carcinoma (SNUC), a rare cancer with a poor prognosis. The patient was treated with crizotinib, a tyrosine kinase inhibitor that targets c-MET, and experienced a complete response. Our report demonstrates the potential of employing precision oncology approaches in SNUC and other rare cancers.

Clinical Implication of Diagnostic and Histopathologic Discrepancies in Sinonasal Malignancies.

OBJECTIVES: To evaluate the incidence of histopathologic diagnostic discrepancy for patients referred to our institution, identify pathologies susceptible to diagnostic error, and assess the impact on survival of histopathologic diagnostic discrepancies. METHODS: Three hundred ninety-seven patients with sinonasal cancers were identified, and discordance between the outside pathologic report and MD Anderson Cancer Center pathologic report was assessed. Overall survival and disease-specific survival were analyzed using Kaplan-Meier and log rank methods. RESULTS: Discordance of major histopathologic diagnoses was present in 24% (97 of 397) of reports, with sinonasal undifferentiated carcinoma, sarcoma, neuroendocrine carcinoma, and poorly differentiated carcinoma pathologies having the highest change in diagnosis (P < .01). A further 61% (244 of 397) had minor changes such as histologic grade, subtype, or stage, with sarcoma and neuroendocrine carcinoma pathologies being most susceptible to change (P < .02). Overall, the 5-year overall survival (OS) and disease-specific survival (DSS) was reduced in patients with a major change in histopathologic diagnosis (59.2% vs. 70.2% (P = .02) and 72.9% vs. 81.2% (P = .02), respectively). Furthermore, patients with a major change in diagnosis and prior treatment experienced a significant reduction in 5-year OS (61.9% vs. 70.4%, P = .03 < .01) and DSS (72.4% vs. 81.5%, P = .04). CONCLUSION: Histopathological diagnosis of sinonasal tumors is complex and challenging given the rarity of the disease. Obtaining the correct diagnosis is important for treatment selection and survival. In histologies prone to misdiagnoses, obtaining a second opinion from experienced head and neck pathologists at a high-volume institution may potentially lead to a change in treatment recommendations that could result in improved survival in patients with sinonasal malignancies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1468-E1475, 2021.