Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.

PURPOSE: The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma. METHODS: Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups. RESULTS: This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA) physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups. CONCLUSIONS: Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic.

Anterolateral keyhole transorbital routes to the skull base: a comparative anatomical study.

OBJECTIVE: Although keyhole transorbital approaches are gaining traction, their indications have not been adequately studied comparatively. In this study the authors have defined them also as transwing approaches-meaning that they use the different facies of the sphenoid wing for cranial entry-and sought to compare the four major ones: 1) lateral orbitocraniotomy through a lateral canthal incision (LatOrb); 2) modified orbitozygomatic approach through a palpebral incision (ModOzPalp); 3) modified orbitozygomatic approach through an eyebrow incision (ModOzEyB); and 4) supraorbital craniotomy through an eyebrow incision (SupraOrb), coupled with its expanded version (SupraTransOrb). METHODS: Cadaveric dissections were performed at the neuroanatomy lab. To delineate the skull base exposure, four formalin-fixed heads were used, with two sides dedicated to each approach. The outer limits were assessed via image guidance and were mapped and illustrated accordingly. A fifth head was dissected purely endoscopically, just to facilitate an overview of the transwing concept. Qualitative features were also rigorously examined. RESULTS: The LatOrb proves to be more versatile in the middle cranial fossa (MCF), whereas the anterior cranial fossa (ACF) exposure is limited to a small area above the sphenoid ridge. An anterior clinoidectomy is possible; however, the exposure of the roof of the optic canal is suboptimal. The ModOzPalp adequately exposes both the ACF and MCF. Its lateral trajectory allows the inferior to superior view, yet there is restricted access to the medial anterior skull base (olfactory groove). The ModOzEyB also provides extensive exposure of the ACF and MCF, but has a more superior to inferior trajectory compared to the ModOzPalp, making it more appropriate for pathology reaching the medial anterior skull base or even the contralateral side. The anterior clinoidectomy is performed with improved visualization of the optic canal. The SupraOrb provides mainly anterior cranial base exposure, with minimal middle fossa. An anterior clinoidectomy can be performed, but without any direct observation of the superior orbital fissure. Some MCF access can be accomplished if the lateral sphenoid wing is drilled inferiorly, leading to its highly versatile variant, the SupraTransOrb. CONCLUSIONS: All the aforementioned approaches use the sphenoid wing as skull base corridor from a specific orientation point; hence these are designated as transwing approaches. Their peculiarities mandate careful case selection for the effective and safe completion of the surgical goals.

Anesthetic recovery outcomes after 2 methods of nasal mucosal preparation for endoscopic sinus surgery.

PURPOSE: Our institution uses two approaches for nasal mucosal preparation during endoscopic sinus surgery (ESS) to improve surgical field visualization: topical epinephrine (TE) versus topical cocaine with injection of lidocaine containing epinephrine (TCLE). We aimed to compare anesthetic outcomes after ESS using these techniques. METHODS AND MATERIALS: We retrospectively identified adult patients at our institution who underwent ESS from May 2018 through January 2023 under general anesthesia with propofol and remifentanil infusions. Postoperative anesthetic outcomes, including pain and recovery time, were compared between patients who had mucosal preparation with TE versus TCLE using inverse probability of treatment weighting (IPTW) to adjust for potential confounders. RESULTS: Among 1449 patients who underwent ESS, 585 had TE, and 864 had TCLE. Compared with TE, during anesthetic recovery, the TCLE group had fewer episodes of severe pain (numeric pain score ≥ 7) (IPTW-adjusted odds ratio, 0.65; 95 % CI, 0.49-0.85; P = .002), less opioid analgesic administration (IPTW-adjusted odds ratio, 0.55; 95 % CI, 0.44-0.69; P < .001), and shorter recovery room stay (IPTW-adjusted ratio of the geometric mean, 0.90; 95 % CI, 0.85-0.96; P = .002). Postoperative nausea and vomiting and postoperative sedation were similar between groups. CONCLUSIONS: Patients who received preparation of the nasal mucosa with TCLE, compared with TE, were less likely to report severe pain or receive an opioid analgesic in the postanesthesia recovery room and had faster anesthetic recovery. This observation from our large clinical practice indicates that use topical and local anesthetic during endoscopic sinus surgery may have benefit for ambulatory ESS patients.

Triple Layer Oronasal Fistula Repair Using Local Endonasal Flaps: Case Series of Three Patients.

Oronasal fistula (ONF) is a common complication encountered after palatoplasty. Repair is indicated when symptoms impact speech and swallowing. In spite of the variety of surgical approaches described to repair these defects, recurrence rates remain high. Traditionally, successful closure is said to be achieved in using a double-layered approach due to the three-dimensional aspect of the defect. The extent of the fistula into the nasal cavity has incited an increased curiosity in using local endonasal flaps. In recent years, endonasal reconstructive procedures have seen increased interest and application, from cranial base defect repairs to orbital reconstruction and beyond. The nasoseptal (NSF) and inferior turbinate flaps (ITF) possess a robust arterial supply and an exceptional reach with excellent results demonstrated in large defect repair. However, the use of these flaps in ONF repair is scarcely discussed in the literature, and their effectiveness is relatively undetermined. In this manuscript, we present a series of three patients who underwent a triple layer ONF closure, with the oral portion incorporating a turn-in mucosal flap plus a local palate rotation flap or greater palatine artery pedicled-rotation flap, and a NSF or an ITF for the nasal portion of the defect.

Combined endoscopic endonasal transpterygoid and sublabial transmaxillary approaches for a large infratemporal fossa trigeminal schwannoma.

BACKGROUND: Trigeminal schwannomas (TSs) with solitary extracranial location are rare, and surgical excision is challenging. In recent years, the endoscopic endonasal transmaxillary transpterygoid approach (EETPA) has been advocated as an effective strategy for TSs in the infratemporal fossa (ITF). METHOD: We describe the steps of the EETPA combined with the sublabial transmaxillary approach for the surgical excision of a giant mandibular schwannoma of the ITF. Indications, advantages, and approach-specific complications are also discussed. The main surgical steps are shown in an operative video. CONCLUSION: A combined EETPA and sublabial transmaxillary approach represents a safe and effective option for the surgical excision of extracranial TSs.

Surgical outcomes of medically failed prolactinomas: a systematic review and meta-analysis.

PURPOSE: In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy. METHOD: A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically. RESULTS: 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I2 = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I2 = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I2 = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I2 = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I2 = 86.34%). CONCLUSIONS: This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.

Skull Base Tumors: Therapeutic Challenges and Multi-Disciplinary Care.

This special edition of Cancers, focusing on skull base tumors, highlights the unique pathologies affecting this anatomic location, as well as the multidisciplinary care necessary to treat these tumors [...].

Outcomes of Immunotherapy in Sinonasal Mucosal Melanoma Patients With Recurrent and Metastatic Disease.

Sinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One-year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%-60.9%), with a median survival of 2.8 years (95% CI: 2.0-5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12-0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02). LEVEL OF EVIDENCE: Level IV.

Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review.

OBJECTIVE: The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events. DATA SOURCES: Embase, Cochrane, Scopus, and Web of Science. REVIEW METHODS: The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023. RESULTS: A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's. CONCLUSION: ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease.

American Rhinologic Society expert practice statement part 2: Postoperative precautions and management principles following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts' opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs.

American Rhinologic Society expert practice statement part 1: Skull base reconstruction following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs.

Carotid Plexus Sympathetic Nerves as a Landmark for the Abducens Nerve Within the Cavernous Sinus During Endoscopic Endonasal Surgery: Cadaveric Anatomic Study and Surgical Consideration.

BACKGROUND AND OBJECTIVES: The abducens nerve (CN VI) is vulnerable to injury during endoscopic endonasal transcavernous surgery. In this study, the authors aimed to develop the surgical anatomic landmark and explore the relationship between the sympathetic nerves (SNs) around the internal carotid artery (ICA) and CN VI within the cavernous sinus (CS). METHODS: The relationship and patterns between the SNs and CN VI were investigated in 15 cadaveric specimens. The intraoperative examples of anatomic landmark were presented. RESULTS: There were SNs around the ICA running into the CN VI, classified into ascending SNs and accessory sympathetic branches. The ascending SNs were divided into 3 types: (1) Type I had a single ascending SN. There were 2 subtypes of Type I (Type IA [17/30, 56.7%] was defined as a single ascending branch that ran into the CN VI, and Type IB [4/30, 13.3%] was defined as a single ascending branch with a terminal bifurcation before merging into the CN VI or lateral CS wall), (2) Type II (7/30, 23.3%) was defined as 2 ascending branches that ran into the CN VI and the lateral CS wall, and (3) Type III (2/30, 6.7%) was defined as 3 ascending branches that ran into the CN VIs and the lateral wall of the CS. The accessory branches of the SNs were defined by sympathetic branches from the posterior genu or horizontal ICA and found in 6/30 sides (20%). CONCLUSION: The authors propose a classification of the relationship between paraclival ICA SNs and the CN VI within the CS, as approached during endoscopic endonasal surgery. The consistent relationship of the ascending SN and CN VI within the CS provides a reliable anatomic landmark during the endonasal approach to the CS.

Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation.

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.

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.

The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review.

BACKGROUND: Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival. METHODS: The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched. RESULTS: Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%). CONCLUSIONS: For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.

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 alone being common. Radiation therapy was administered to 89% of patients. All 3 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.

Patterns of recurrence and disease progression in patients with positive-margin olfactory neuroblastoma following primary resection.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS: The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS: Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.