Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

OBJECTIVE: This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS: The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS: In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

Predicting the need for occipitocervical fusion for patients with lower clival chordoma: a single-center retrospective study.

OBJECTIVE: To assess the impact of tumor extension into the occipital condyle (OC) in lower clival chordoma management and the need for occipito-cervical fusion (OCF). METHODS: A retrospective analysis was conducted on 35 patients with lower clival chordoma. The preoperative area of the intact OCs, Hounsfield units, and the integrity of the apical ligament and the tectorial membrane were assessed using preoperative imaging. RESULTS: Seven (20%) patients were in the OCF group. The OCF group exhibited a higher prevalence of preoperative pain in the neck or head (p = 0.006), ligament absence (p = 0.022), and increased propensity for postoperative wound issues (p = 0.022) than the non-OCF group. The OCF group had less intact OCs (p < 0.001) and higher spinal instability neoplastic score (p = 0.002) than the non-OCF group. All patients with intact OCs<60% underwent OCF, and those with OCs≥70% were treated without OCF. Those with OCs between 60% and 69% underwent OCF if the ligaments were eroded, and did not undergo OCF if the ligaments were intact. Treatment strategies varied, with endoscopic endonasal approach (EEA) alone being common. Radiation therapy was administered to 89% of patients. All three patients treated with OCF after tumor resection had wound issues; none treated with OCF before resection had wound issues. None developed atlanto-occipital instability. Survival rates did not significantly differ between groups. CONCLUSIONS: In the absence of mobility-related neck pain, patients with lower clival chordoma and intact OC≥60%, intact apical ligament, and intact tectorial membrane, may not require OCF.

The Mayo Clinic Salivary Tissue-Organoid Biobanking: A Resource for Salivary Regeneration Research.

The salivary gland (SG) is an essential organ that secretes saliva, which supports versatile oral function throughout life, and is maintained by elusive epithelial stem and progenitor cells (SGSPC). Unfortunately, aging, drugs, autoimmune disorders, and cancer treatments can lead to salivary dysfunction and associated health consequences. Despite many ongoing therapeutic efforts to mediate those conditions, investigating human SGSPC is challenging due to lack of standardized tissue collection, limited tissue access, and inadequate purification methods. Herein, we established a diverse and clinically annotated salivary regenerative biobanking at the Mayo Clinic, optimizing viable salivary cell isolation and clonal assays in both 2D and 3D-matrigel growth environments. Our analysis identified ductal epithelial cells in vitro enriched with SGSPC expressing the CD24/EpCAM/CD49f+ and PSMA- phenotype. We identified PSMA expression as a reliable SGSPC differentiation marker. Moreover, we identified progenitor cell types with shared phenotypes exhibiting three distinct clonal patterns of salivary differentiation in a 2D environment. Leveraging innovative label-free unbiased LC-MS/MS-based single-cell proteomics, we identified 819 proteins across 71 single cell proteome datasets from purified progenitor-enriched parotid gland (PG) and sub-mandibular gland (SMG) cultures. We identified distinctive co-expression of proteins, such as KRT1/5/13/14/15/17/23/76 and 79, exclusively observed in rare, scattered salivary ductal basal cells, indicating the potential de novo source of SGSPC. We also identified an entire class of peroxiredoxin peroxidases, enriched in PG than SMG, and attendant H2O2-dependent cell proliferation in vitro suggesting a potential role for PRDX-dependent floodgate oxidative signaling in salivary homeostasis. The distinctive clinical resources and research insights presented here offer a foundation for exploring personalized regenerative medicine.

Longitudinal treatment outcomes of recurrent clival chordomas: a single-center retrospective study.

OBJECTIVE: The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. METHODS: A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors' institution between 1990 and 2022. RESULTS: A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. CONCLUSIONS: Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.

Extent of Surgical Resection as a Predictor of Tumor Progression in Skull Base Chordomas: A Multicenter Volumetric Analysis.

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center.

OBJECTIVES: To investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). MATERIALS AND METHODS: Retrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. RESULTS: A total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2-87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6-2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). CONCLUSION: There is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Malignant Carotid Paraganglioma: A Case Report.

Carotid body tumors (CBTs) are rare neoplasms of the neuroectoderm accounting for 0.6% of head and neck tumors, with a 2%-12.5% risk of malignancy. While surgical resection has been associated with a high rate of neurologic and vascular complications, it remains the mainstay of treatment for malignant CBTs. We present the case of a 40-year-old female with a 5-year history of progressively enlarging right-sided neck mass, with MRI and MRA showing a Shamblin grade III CBT encasement of the internal carotid artery (ICA). Blood flow was absent in the petrous segment of ICA, with great collateralization of brain blood supply, enabling en bloc resection of the tumor with a carotid bulb and ligation of the common carotid artery (CCA) without vascular reconstruction. Further, we describe the characteristics and current management for malignant CBTs, including surgical management, pre-surgical embolization, and adjuvant radiation therapy.

Comparison of Tumor Control After Stereotactic Radiosurgery or Pencil Beam Proton Therapy for Newly Diagnosed Clival Chordomas: A Single-Center Retrospective Study.

OBJECTIVE: To compare outcomes of proton radiation therapy (PRT), stereotactic radiosurgery (SRS), and x-ray-based radiation with an SRS boost (XRT + SRS) for newly diagnosed clival chordoma. METHODS: Consecutive patients who underwent PRT or SRS in our facility were retrospectively reviewed. RESULTS: A total of 59 patients were identified (PRT, 36; SRS, 11; XRT + SRS, 12). The mean age (± standard deviation) was 46 ± 20 years, with 54% being male. The mean tumor diameter (± standard deviation) was 3.7 ± 1.5 cm, and 21 (36%) involved the lower clivus. Gross total or near-total resection was attained in 27 patients (46%), all of whom received PRT. PRT was administered with a median prescribed dose of 70.8 Gy (range, 66.0-76.0). SRS involved a median marginal dose of 16 Gy (range, 14-20) and a median maximal dose of 36 Gy (range, 30-45). The XRT + SRS group was treated with an SRS marginal dose of 12.5 Gy (range, 10-20), a maximal dose of 27 Gy (range, 20-40), and an XRT prescription dose of 50.4 Gy (range, 45.0-59.4). Fifteen recurrences were observed (PRT, 6; SRS, 5; XRT + SRS, 4). For the entire cohort (n = 59), recurrence was associated with the degree of resection (P = 0.042), but not with radiation groups (P = 0.98). For patients after subtotal resection or biopsy (n = 32), the SRS ± XRT group was associated with few recurrences (hazard ratio, 0.260; 95% confidence interval, 0.069-0.98; P = 0.046). CONCLUSIONS: Patients after subtotal resection or biopsy may benefit from the incorporation of SRS.

Identification of Deep Cervical Fascial Layers During Anterior Cervical Spine Exposure.

BACKGROUND: Anterior approaches to the cervical spine are among the most common exposures by which neurosurgeons and orthopedic surgeons access the prevertebral space and ultimately the cervical disk and vertebral bodies. There is a paucity of literature describing the microanatomic fascial planes of the neck with respect to anterior cervical approaches. OBJECTIVE: To delineate the microanatomic connections of the cervical fascial planes pertinent to anterior cervical exposure. METHODS: Using a cadaveric model, original illustrations, the Visible Human Project, and an original surgical video, we demonstrate a stepwise method for identifying the correct planes for anterior cervical exposure. RESULTS: A step-by-step method for identifying the anterior cervical fascial planes intraoperatively is demonstrated. CONCLUSION: A comprehensive understanding of anterior cervical microsurgical anatomy is vital for performing a methodical yet efficient approach to the prevertebral space while minimizing retraction and iatrogenic injury to the surrounding neurovascular structures.

Pleomorphic Liposarcoma of the Parapharyngeal Space: A Rare Case Report.

Pleomorphic liposarcomas (PLS) are the rarest subtype of liposarcomas, representing only 5-10% of liposarcomas. Pleomorphic liposarcomas are extremely aggressive and have a poor prognosis. Here, we present the case of a 66-year-old female who presented with difficulty swallowing, talking, and hearing. An extensive investigation revealed the presence of an aggressively growing parapharyngeal space mass. The patient underwent a left parapharyngeal space exploration and left deep lobe parotidectomy by the cervicoparotid approach. Histopathological evaluation of the surgical specimen further confirms the presence of pleomorphic subtype of liposarcoma. The patient received adjuvant radiotherapy following the procedure. At 6 months postop, the patient is in good health and shows no evidence of recurrence. In addition to this treatment, we discuss the radiologic and histologic findings of this current case.

Single-port robotic transcervical long-segment thoracic tracheal reconstruction: Cadaveric proof-of-concept study.

Objective: Slide tracheoplasty is the standard technique to repair congenital long-segment tracheal stenosis. This operation most commonly requires median sternotomy, which has drawbacks in young children. We hypothesized that a transcervical approach without sternotomy would be feasible if done with a single-port robotic system. Methods: This proof-of concept study was performed in 2 small adult cadavers using a single-port robotic surgical system via a small neck incision. Relevant information, including operative time and details of operative technique, were recorded. Results: Long-segment slide tracheoplasty was completed successfully in 2 cadavers using a small neck incision and a single-port robotic surgical system. Strengths and pitfalls of the technique were identified, including technical refinements from the first attempt to the second. Operative time for robotic mobilization, incision, and anastomosis of the trachea was comparable to standard open approaches. Conclusions: Small-incision transcervical slide tracheoplasty, assisted by a single-port surgical robotic system, is feasible in a human cadaver. More work is needed to determine safety and applicability in live patients, particularly in children.

Mayo Clinic Clival Chordoma Case Series: Impact of Endoscopic Training on Clinical Care.

The management of clival chordoma in our group shifted around 2013 to mostly endoscopic, and proton beam was introduced for our multidisciplinary team. Consecutive patients who had surgical resection from 1987 to 2021 were reviewed. A total of 58 patients (39 patients after 2013) were analyzed. The mean tumor size was 3.7 cm, and the most common location was the upper clivus (43%). Compared to before 2013, after 2013, the endoscopic endonasal approach was more common (90%, p < 0.001), and more gross or near total resections (64%, p = 0.002) were attained. Ten cases (17%) were revision surgeries referred from elsewhere, and three cases (5%) underwent additional surgery elsewhere before adjuvant radiation. The postoperative cerebrospinal fluid leak occurred in 7%. Post-operative new cranial nerve deficits occurred in 32% before 2013, compared to 2.6% after 2013 (p = 0.004). For cases before 2013, 10 patients (53%) recurred during the median follow-up of 144 months (mean, 142 months), whereas for cases after 2013, seven patients (18%) recurred with a median follow-up of 35 months (mean, 42 months). 5-year progression-free survival was 58%, and 5-year overall survival was 87%. A specialized multidisciplinary team improved the resection rate compared to a historical cohort with an excellent morbidity profile.

Characterization of Transgenic NSG-SGM3 Mouse Model of Precision Radiation-Induced Chronic Hyposalivation.

Regenerative medicine holds promise to cure radiation-induced salivary hypofunction, a chronic side effect in patients with head and neck cancers, therefore reliable preclinical models for salivary regenerative outcome will promote progress towards therapies. In this study, our objective was to develop a cone beam computed tomography-guided precision ionizing radiation-induced preclinical model of chronic hyposalivation using immunodeficient NSGSGM3 mice. Using a Schirmer's test based sialagogue-stimulated saliva flow kinetic measurement method, we demonstrated significant differences in hyposalivation specific to age, sex, precision-radiation dose over a chronic (6 months) timeline. NSG-SMG3 mice tolerated doses from 2.5 Gy up to 7.5 Gy. Interestingly, 5-7.5 Gy had similar effects on stimulated-saliva flow (∼50% reduction in young female at 6 months after precision irradiation over sham-treated controls), however, >5 Gy led to chronic alopecia. Different groups demonstrated characteristic saliva fluctuations early on, but after 5 months all groups nearly stabilized stimulated-saliva flow with low-inter-mouse variation within each group. Further characterization revealed precision-radiation-induced glandular shrinkage, hypocellularization, gland-specific loss of functional acinar and glandular cells in all major salivary glands replicating features of human salivary hypofunction. This model will aid investigation of human cell-based salivary regenerative therapies.

Long-Term Toxic Effects, Swallow Function, and Quality of Life on MC1273: A Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in Human Papillomavirus-Positive Oropharyngeal Cancer.

PURPOSE: Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes. METHODS AND MATERIALS: Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally. RESULTS: Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy-dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL. CONCLUSIONS: De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL.

Parotid sebaceous lymphadenoma associated with Sjogren's syndrome: Review of pathologic and radiologic characteristics and clinical presentation.

Salivary lymphadenoma is an extremely rare neoplasm that is usually seen in the older patient population, arising sporadically on one side and almost exclusive to the parotid gland. Imaging and pathology findings can mimic both benign and malignant tumors, and therefore, this lesion may be misdiagnosed if not on the differential diagnosis. This article reviews the clinical presentation, as well as the pathology and imaging findings of salivary lymphadenoma in the setting of Sjogren's syndrome.

The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review.

PURPOSE: Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. MATERIALS & METHODS: Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. RESULTS: 75 patients with median follow-up time of 47 months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5 years were 71% and 60% respectively. CONCLUSION: Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.

Induction Therapy Prior to Surgical Resection for Patients Presenting with Locally Advanced Esthesioneuroblastoma.

Esthesioneuroblastoma (ENB) is a rare olfactory malignancy that can present with locally advanced disease. At our institution, patients with ENB in whom the treating surgeon believes that a margin-negative resection is initially not achievable are selected to undergo induction with chemotherapy with or without radiotherapy prior to surgery. In a retrospective review of 61 patient records, we identified six patients (10%) treated with this approach. Five of six patients (83%) went on to definitive surgery. Prior to surgery, three of five patients (60%) had a partial response after induction therapy, whereas two of five (40%) had stable disease. Microscopically margin-negative resection was achieved in four of five (80%) of the patients who went on to surgery, while one patient had negative margins on frozen section but microscopically positive margins on permanent section. Three of five patients (60%) recurred after surgery; two of these patients died with recurrent/metastatic ENB. In summary, induction therapy may facilitate margin-negative resection in locally advanced ENB. Given the apparent sensitivity of ENB to chemotherapy and radiotherapy, future prospective studies should investigate the optimal multidisciplinary approach to improve long-term survival in this rare disease.

Sinonasal Osteosarcoma: Report of 14 New Cases and Systematic Review of the Literature.

Objective The objective of this study is to describe the clinical presentation, tumor characteristics, natural history, and treatment patterns of sinonasal osteosarcoma. Methods Fourteen patients who had been treated for osteosarcoma of the nasal cavity and paranasal sinuses at a tertiary care center were reviewed. In addition, a systematic review of the literature for osteosarcoma of the sinonasal cavity was performed. Results In a systematic review, including 14 patients from the authors' institution, 53 total studies including 88 patients were assessed. Median follow-up was 18 months (interquartile range: 8-39 months). The most common presenting symptoms were facial mass or swelling (34%), and nasal obstruction (30%). The most common paranasal sinus involved by tumor was the maxillary sinus (64%), followed by the ethmoid sinuses (52%). The orbit (33%), dura (13%) and infratemporal fossa (10%) were the most common sites of local invasion. The majority of patients underwent surgery followed by adjuvant therapy (52.4%). Increasing age was associated with decreased overall survival rate (unit risk ratio [95% confidence interval (CI)] = 1.02 [1.003-1.043]; p = 0.0216) and T4 disease was associated with decreased disease-specific survival rate (hazard ratio [HR] = 2.87; p = 0.0495). The 2- and 5-year overall survival rates were 68 and 40%, respectively, while 2- and 5-year disease-specific survival rates were 71% and 44%, respectively. Conclusion Sinonasal osteosarcomas are uncommon tumors and can pose a significant therapeutic challenge. Increasing age and T4 disease are associated with worse prognosis. This disease usually warrants consultation by a multidisciplinary team and consideration of multimodality therapy.

Delaying Postoperative Radiotherapy in Low-Grade Esthesioneuroblastoma: Is It Worth the Wait?

Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate ( p = 0.23), time to DP ( p = 0.26), or the local tumor control rate ( p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.