Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be ...determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC.
Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation.
A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 95% CI, 2.89 to 9.36).
In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.
Sinonasal tumors are a rare heterogenous group of pathologies with poor prognosis. In recent years better definition and understanding of histology, molecular classification, biological behavior and ...advances in therapy have resulted in improved prognosis. The purpose of this review is to give an updated summary of the recent advances in treatment, and where relevant, with references to pathology classifications.
Recent publications highlight the role of induction chemotherapy and advances in radiotherapy in advanced cancers. In addition, better understanding of genomics and histology specific treatment algorithms has led to more tailored treatment approaches. The role of immunotherapy and targeted therapy are yet to be explored.
This review gives an up to date summary of the advances in contemporary management strategies for locally advanced sinonasal malignancies and can serve as a guide for researchers and clinicians.
Background
In this study, we evaluate our experience and the outcomes of patients with sinonasal cancer treated with endoscopic resection.
Methods
Retrospective review of patients with sinonasal ...cancer who had endoscopic resection was conducted. The outcomes of interest included survival outcomes and surgical complications.
Results
Overall, 239 patients were included. Median follow up time was 46.6 months. Of the 239 patients, 167 (70%) had a pure endonasal endoscopic approach, while 72 (30%) had an endoscopic‐assisted approach. Postoperative cerebrospinal fluid (CSF) leakage occurred in 14 patients (5.9%). Negative margins were achieved in 209 patients (87.4%). There was no significant difference in the margin status between the pure endoscopic and endoscopic‐assisted group (P = .682). There was no significant difference in the survival outcomes between both the groups.
Conclusion
Our data suggest that in properly selected patients, endoscopic approaches have acceptable morbidity with low complication rates and can provide an oncologically sound alterative to open approaches.
Histone modification patterns and their combinatorial readout have emerged as a fundamental mechanism for epigenetic regulation. Here we characterized Spindlin1 as a histone effector that senses a ...cis-tail histone H3 methylation pattern involving trimethyllysine 4 (H3K4me3) and asymmetric dimethylarginine 8 (H3R8me2a) marks. Spindlin1 consists of triple tudor-like Spin/Ssty repeats. Cocrystal structure determination established concurrent recognition of H3K4me3 and H3R8me2a by Spin/Ssty repeats 2 and 1, respectively. Both H3K4me3 and H3R8me2a are recognized using an "insertion cavity" recognition mode, contributing to a methylation state-specific layer of regulation. In vivo functional studies suggest that Spindlin1 activates Wnt/β-catenin signaling downstream from protein arginine methyltransferase 2 (PRMT2) and the MLL complex, which together are capable of generating a specific H3 "K4me3-R8me2a" pattern. Mutagenesis of Spindlin1 reader pockets impairs activation of Wnt target genes. Taken together, our work connects a histone "lysine-arginine" methylation pattern readout by Spindlin1-to-Wnt signaling at the transcriptional level.
Objectives/Hypothesis
Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long‐term outcomes of ...patients with ONB and to determine the factors associated with prognosis.
Study Design
Retrospective study.
Methods
A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan–Meier curves were utilized to assess survival.
Results
Median follow‐up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five‐year overall survival and disease‐specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P = .003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival.
Conclusion
ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long‐term surveillance.
Level of Evidence
Level 4 Laryngoscope, 132:290–297, 2022
Expanded endoscopic approaches (EEAs) are increasingly used for the definitive management of sinonasal malignancies. EEAs, in appropriately selected cases, provide similar oncological outcomes but ...are associated with lower complication rates compared with open surgical approaches. Selection bias is a limitation reported in previous studies comparing EEAs and open surgical approaches for the management of sinonasal malignancies. To address this issue, in this study the authors compared the long-term oncological outcomes of an anatomically matched cohort of patients with locally advanced sinonasal malignancies with skull base involvement (T4 stage). The specific objective of this study was to investigate the extent of resection (EOR), overall survival (OS), and disease progression between the EEA and open surgical cohorts.
A cohort of 42 patients with locally advanced sinonasal malignancies and skull base involvement (stage T4) and operated on via an EEA was matched anatomically with a cohort of 54 patients who had undergone open surgery. A retrospective chart review was conducted on these 96 patients who were treated between September 1993 and June 2020. All patients in the cohort were eligible for either an EEA or open surgery according to anatomical criteria. Patients of all ages were included, and the minimum follow-up required for eligibility was 4 months. Patients were excluded if surgery was not offered for curative intent and preoperative imaging did not demonstrate that gross-total resection was achievable.
There were more complications in the conventional surgery cohort than in the EEA cohort (33.33% vs 14.29%, p = 0.033). There was no significant difference in the EOR between the EEA and conventional surgery cohorts, as demonstrated by comparable rates of positive margins in both groups (5.56% vs 2.38%, respectively). Disease progression (hazard ratio HR 0.47, 95% CI 0.17-1.27, p = 0.137) was lower and OS (HR 0.58, 95% CI 0.26-1.29, p = 0.183) was higher in the EEA cohort, but these findings did not reach statistical significance.
The EEA was found to be associated with lower risks of complications than conventional craniofacial surgical approaches. There were no significant differences in OS and progression-free survival between the EEA and conventional surgical cohorts when comparing anatomically matched cohorts of patients with stage T4 sinonasal malignancies and skull base involvement.
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.
Results from this study demonstrate a favorable response to induction chemotherapy in patients with squamous cell carcinoma of the paranasal sinuses. The data suggest that a response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation.
Abstract
Introduction
Malignant sinonasal tumors comprise less than 1% of all neoplasms. A wide variety of tumors occurring primarily in this site can present with an undifferentiated or poorly ...differentiated morphology. Among them are esthesioneuroblastomas, sinonasal undifferentiated carcinomas, and neuroendocrine carcinomas.
Objectives
We will discuss diagnostic strategies, recent advances in immunohistochemistry and molecular diagnosis, and treatment strategies.
Data Synthesis
These lesions are diagnostically challenging, and up to 30% of sinonasal malignancies referred to the University of Texas MD Anderson Cancer Center are given a different diagnosis on review of pathology. Correct classification is vital, as these tumors are significantly different in biological behavior and response to treatment. The past decade has witnessed advances in diagnosis and therapeutic modalities leading to improvements in survival. However, the optimal treatment for esthesioneuroblastoma, sinonasal undifferentiated carcinoma, and neuroendocrine carcinoma remain debated. We discuss advances in immunohistochemistry and molecular diagnosis, diagnostic strategies, and treatment selection.
Conclusions
There are significant differences in prognosis and treatment for esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Recent advances have the potential to improve oncologic outcomes but further investigation in needed.
Introduction
Sinonasal tumors that harbor neuroendocrine histologic features include olfactory neuroblastoma (previously known as esthesioneuroblastoma), sinonasal neuroendocrine carcinoma, and ...sinonasal undifferentiated carcinoma. These tumors represent a diverse spectrum of clinical behavior and as such require histology-specific management. Herein, we review the management of these sinonasal tumors with neuroendocrine features and discuss fundamentals of multi-modality care for each histology. An emphasis is placed on olfactory neuroblastomas, given their relative frequency and skullbase origin.
Methods
A comprehensive literature review on contemporary management of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma was performed.
Results
Management of sinonasal tumors with neuroendocrine features can include surgical resection, radiation therapy, and/or chemotherapy. Due to their site of origin, these tumors can frequently involve the skullbase, which can require site-specific care. The optimal treatment modalities and the sequence in which they are performed are largely dependent on histology. In most cases, olfactory neuroblastoma is best managed with surgical resection followed by radiation therapy. Sinonasal neuroendocrine carcinomas represent a variety of histologic phenotypes (carcinoid, atypical carcinoid, small cell, and large cell), which determine the optimal treatment modality. Finally, sinonasal undifferentiated carcinoma is likely best managed by induction chemotherapy with subsequent therapy dictated by the initial response.
Conclusions
A team approach to multi-modality care is essential in the treatment of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Early biopsy, histologic diagnosis, and comprehensive imaging are critical to determining the appropriate management paradigm.
Sinonasal cancer is a heterogeneous orphan disease of diverse histologies, each with distinct clinical, oncologic, and toxicity profiles. Because of the comparative rarity of these cancers, sinonasal ...cancers are treated as a grouped diagnosis despite their clinical and biological heterogeneity. Multimodality treatment with a combination of surgery, chemotherapy, and/or radiotherapy is the standard‐of‐care for advanced‐stage patients but there are few surveillance or follow‐up practice guidelines or formalized survivorship care pathways. A scoping literature review was conducted via PubMed, EMBASE, and Google Scholar. A total of 112 studies were included, which were grouped along the following topics: surveillance, second primary tumors, quality of life, and symptom burden. Sinonasal cancer tends to exhibit a higher rate of local failure and occur in a delayed fashion compared to mucosal malignancies of the head and neck. Moreover, the site of failure and time‐varying risk of recurrence is histology‐specific. Following multimodality treatment of the skull base, patients may experience endocrine, visual, auditory, sinonasal, olfactory, and neurocognitive deficits, as well as psychosocial impairments that impact multiple physical and neuropsychological domains, resulting in diminished quality of life. Sinonasal cancer patients would benefit from tailored, histology‐specific survivorship programs to address the recurrence, second primary, and functional impairments resulting from disease and treatment toxicity.
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