Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

PURPOSE: In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). METHODS: 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. RESULTS:  Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of 61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). CONCLUSIONS: The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Multimodal treatment and immune checkpoint inhibition in sinonasal mucosal melanoma: real-world data of a retrospective, single-center study.

PURPOSE: Local failure and distant metastases occur frequently in sinonasal mucosal melanoma (SNMM). Response rates to chemotherapy are low and targetable mutations are rarely detected. However, there is increasing data indicating efficacy of immune checkpoint inhibition (ICI). The aim of this retrospective monocenter study was to assess the mutational landscape and to evaluate the outcome of surgical treatment and ICI in SNMM in a real-world setting. METHODS: Thirty-eight SNMM patients being treated between 1999 and 2020 at our institution were retrospectively reviewed. Survival curves were generated according to Kaplan-Meier and compared by the log-rank test. RESULTS: Local failure was seen in 60% of patients treated in a curative intent. Overall, 24% of all patients suffered from regional and 66% from distant metastases. Next generation sequencing revealed mutations of BRAF, NRAS and KRAS. One out of three patients treated with a primary ICI showed a complete response (CR) and two showed progressive disease. Eleven patients received ICI as a palliative treatment. CR could be observed in three patients and stable disease in one patient. In the whole study population, the 5-year overall survival rate (OS) was 26%. OS was better for patients who received ICI during the course of disease. CONCLUSIONS: Recurrences and distant metastases are frequent in SNMM. Durable CR could be observed after primary and palliative ICI. Therefore, ICI in a palliative, adjuvant or even neoadjuvant setting might play a promising role in SNMM therapy while targetable mutations are rarely detected.

Treatment for SMARCB1 (INI-1) deficient sinonasal tumor: a single-institution study.

Currently, less than 200 cases of SMARCB1-deficient sinus cancer (SDSC) have been documented. Little information is available about the best treatment options or prognosis for SDSC. From September 2016 to November 2022, the medical records of 22 people with SDSC were evaluated retrospectively. Patient demographics, staging, pathology findings, treatment details, recurrence, metastasis, and survival outcomes were all investigated by the researchers. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort were 89.8%, 84.2%, and 45.1%, respectively, as were the 1-, 2-, and 3-year progression-free survival (PFS) rates of 81.8%, 63.8%, and 31.9%. After induction chemotherapy, 66.7% (10/15) of patients exhibited decreased tumor volume. Patients who accepted chemoradiotherapy had a better 2-year OS (100% vs. 72.7%, p=0.048) than those who accepted surgery as a preference. However, there is no difference in 2-year PFS between the two groups (53.0% vs. 75.8%, p=0.59). Patients with progressed or stable disease after induction chemotherapy had a higher risk of developing local recurrence (p=0.007); they also showed poor 2-year PFS (40.0% vs. 82.1%, p=0.019). SDSC had a poor 3-year OS, with a PFS of less than 50%. For locally advanced SDSC, chemoradiotherapy might be managed before surgery, especially in patients who benefit from induction chemotherapy.

Therapeutic efficacy of intra-arterial docetaxel and nedaplatin infusion concomitant with radiotherapy for T4 maxillary sinus squamous cell carcinoma.

The aim of this study was to evaluate the efficacy of intra-arterial chemoradiotherapy with docetaxel and nedaplatin for T4 maxillary sinus squamous cell carcinoma (MSSCC). Data were retrospectively analysed for 22 consecutive patients with T4 MSSCC who underwent intra-arterial chemoradiotherapy. Participants received intensity-modulated radiotherapy (70 Gy in 35 fractions) concomitantly with docetaxel (60 mg/m2) and nedaplatin (80 mg/m2) administered every 4 weeks for a total of three sessions. The median follow-up period was 49 months (range 12-91 months). T4a tumours were found in 16 patients (73%) and T4b tumours in six patients (27%). Cervical metastasis was found in nine patients (41%; five N2b, four N2c). The 5-year loco-regional control, disease-free survival, and overall survival rates for patients with T4a disease were 92.3%, 92.3%, and 90.3%, respectively, compared to 83.3% (P = 0.42), 66.7% (P = 0.07), and 83.3% (P = 0.46), respectively, for those with T4b disease. The 5-year loco-regional control, disease-free survival, and overall survival rates for patients with cervical lymph node metastasis were all 87.5% compared to 92.3% (P = 0.86), 84.6% (P = 0.69), and 92.3% (P = 0.93), respectively, for those without cervical metastasis. Intra-arterial chemoradiotherapy with docetaxel and nedaplatin may provide favourable loco-regional control and increased survival in T4 MSSCC.

Sinonasal cancers treatments: state of the art.

PURPOSE OF REVIEW: The present review provides the reader with the state-of-the-art concepts of sinonasal oncology in view of the latest literature data. RECENT FINDINGS: 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. SUMMARY: 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.

Neoadjuvant chemotherapy for locoregionally advanced squamous cell carcinoma of the paranasal sinuses.

BACKGROUND: Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. METHODS: The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. RESULTS: The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). CONCLUSIONS: The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

Cetuximab and paclitaxel combination therapy for recurrent basaloid squamous cell carcinoma in the ethmoid sinus.

Basaloid squamous cell carcinoma (BSCC), a histologically distinctive variant of squamous cell carcinoma comprising basal cell carcinoma and squamous cell carcinoma, is aggressive and shows a poor prognosis because of frequent lymph node invasion and distant metastases. To date few articles regarding chemotherapy for metastatic disease have been reported, thus feasible chemotherapy is not well established. Cetuximab is a monoclonal antibody for epithelial growth factor receptor (EGFR), which has great efficacy for head and neck squamous cell carcinoma due to EGFR signaling pathway blockage. Because BSCC also highly expresses EGFR, cetuximab may be effective for BSCC. We report here a first case of recurrent BSCC in the ethmoid sinus with intracranial extension treated with cetuximab-based chemotherapy, which revealed great response in a 40-year-old man. Positron emission tomography (PET) revealed no lymph node or distant metastasis. The patient underwent chemoradiotherapy 66 Gy in 33 fractions with triweekly 100 mg/m2 cisplatin. However, 12 weeks after treatment completion PET revealed a residual tumor at the primary cancer site. Combination therapy with weekly paclitaxel and cetuximab was started, and complete response was observed 2 months from treatment initiation. The patient has maintained complete response for 32 months, and no tumor regrowth has been observed.

Treatment sequence of cetuximab and immune checkpoint inhibitor in head and neck squamous cell carcinoma differentially affects outcomes.

OBJECTIVES: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed. RESULTS: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen. CONCLUSION: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy.

A rare case of cerebral hemorrhage associated with intra-arterial infusion chemotherapy for advanced sphenoid sinus cancer.

Central nervous damage related to intra-arterial infusion chemotherapy (IAC) for head and neck cancer reported to date are cerebral infarction, transient ischemic attack, and neuropathy. There have been no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Authors report a case that underwent intra-arterial infusion chemoradiotherapy for advanced sphenoid sinus cancer which extended to the left cavernous sinus and cranium, subsequently suffered cerebral hemorrhage thought to have been caused by IAC. Treatment should be performed with greater caution when the head and neck cancer involves the cavernous sinus or cranium, as in the present case.

Extra-skeletal Ewing's sarcoma of the frontal sinus: a rare disorder in pediatric age.

Paediatric sinonasal tumours comprise numerous aetiologies. Ewing's sarcoma (ES) consists of a malignancy of neuroectodermal origin. This type of sarcoma affects mainly children and adolescents and can assume the skeletal or extra-skeletal form. Primary ES of head and neck is extremely rare, accounting for only 4%-9% of all cases. So far, as much as we know, only a few cases of sinonasal ES have been reported in literature. The authors present a case of a previous healthy 12-year-old girl who presented with a rapidly growing and expansive frontal mass and unilateral nasal obstruction. Immunohistochemical, molecular and cytogenetic analysis of the lesion showed diffuse expression of CD56 and CD99 on tumour cells and a translocation involving chromosome 22q12, confirming ES diagnosis.

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report.

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907-910, 2020.