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This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors.This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory HeadNeck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference.Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48-22.88; p = 0.012) and moderate (OR, 30.01; 95% CI; 7.96-113.10; p 0.001) hearing loss and tinnitus were associated with higher odds of reporting moderate to severe symptom interference scores in comparison to no hearing loss and tinnitus. This association of hearing dysfunction was consistent with all domains of HRQoL.Our findings provide preliminary evidence to support the need for continued audiological evaluations and surveillance to detect hearing dysfunction, to allow for early management and to alleviate the long-term impact on QoL.

Supplementary Table from Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck

Supplementary Figure from Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck

Purpose:In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence.Patients and Methods:Newly diagnosed or recurrent stage III–IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response.Results:Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9–54.3] had partial responses by RECIST, 15 patients (75%; 95% CI, 50.9–91.3) had a pCR (n = 11) or MPR (n = 4). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7–26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9–100), 89.5% (95% CI, 76.7–100), and 95% (95% CI, 85.9–100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR.Conclusions:Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.

To introduce a minimally invasive and image-guided technique for staged placement of a percutaneous abutment after osseointegrated implantation.Adults undergoing temporal bone resection at two academic medical centers.Ultrasound-guided percutaneous installation of a bone conduction hearing device abutment. All patients had lateral temporal bone resection with osseointegrated implantation. Abutment placement followed as a planned staged procedure 3 to 6 months later depending on the use of radiotherapy.Ability to use a bone conduction hearing device and occurrence of skin reactions or wound complications.Twelve patients successfully underwent abutment installation through a 5 mm skin biopsy punch incision, nine of which had minimal to no skin reaction surrounding the abutment. Two patients developed Holgers grade 1 skin reaction (redness with slight swelling). One patient experienced an osseointegration failure 152 days after abutment placement.Ultrasound is a widely available imaging modality that can be used to precisely localize subcutaneous osseointegrated implants, allowing for minimally invasive percutaneous placement of an abutment under local or general anesthesia.

Objective To determine recurrence patterns in patients with head and neck cancers requiring facial nerve sacrifice and to determine the optimal management of the positive proximal facial nerve margin. Study design Case series with chart review. Setting Tertiary care center. Patients One hundred fifty-five patients with head and neck malignancies who underwent sacrifice of the facial nerve between March 1, 1999 and October 31, 2020. Demographics, preoperative facial nerve function, prior oncologic treatment, histologic type, operative details, adjuvant treatment, recurrence patterns, and overall survival were reviewed. Main outcome measures Recurrence rates and recurrence location. Results Thirteen patients (8%) had positive proximal margins on final pathologic evaluation. Six of 13 (46%) experienced disease recurrence. No disease recurred proximally along the facial nerve. The recurrence rate was 26% for negative proximal facial nerve margins. Segments of the facial nerve biopsied included: extratemporally (n = 78), at the stylomastoid foramen (36), mastoid segment (22), second genu (7), tympanic (6), geniculate (3), labyrinthine (1), and IAC (2). Median patient follow-up was 30.3 months. Conclusions Our data suggest that a conservative approach to a positive proximal facial nerve margin is optimal with respect to operative planning, patient morbidity, and disease recurrence patterns. Recurrence proximally along the facial nerve is an exceedingly rare event and the necessity of biopsy proximal to the geniculate ganglion, and in some cases even to the second genu, is called into question.

OBJECTIVES/HYPOTHESIS To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease's natural history, prognostic factors, management, and outcomes. STUDY DESIGN Retrospective chart review. METHODS Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease. RESULTS TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, three-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful. CONCLUSIONS TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2578-2585, 2021.

Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear.Retrospective analysis.We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021.We report the largest series of patients with MF involving the external ear and EAC. Of the 40 patients included in this study, 17 presented with Mycosis Fungoides in the otologic region (MFO). Of these 17 MFO patients, 2/17 had involvement of the external ear only, 3/17 of the EAC only, 11/17 of both the external ear and EAC, and 1/17 of the periauricular skin. Of note, 11/14 (79%) patients presenting with EAC disease died compared to11/26 (42%) of patients without involvement. In addition, eight of the 13 (62%) patients with external ear involvement died compared to 14/27 (52%) of patients without involvement. Ear canal involvement was associated with a statistically significant shorter overall survival duration in patients with MF (p = 0.03). Furthermore, disease in the EAC was found to have a hazard ratio value of 2.565 (CI 1.102-5.970).Involvement of the EAC by MF portends a poor prognosis. This finding highlights the need for a more in-depth otologic evaluation of patients with MF.Level 4 Laryngoscope, 2022.

OBJECTIVE Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma. METHODS All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors’ institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes. RESULTS Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence. CONCLUSIONS The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

This report describes osteoblastoma of the temporal bone found on a well-child visit. The relevant clinical, radiographic, and histologic features are described. The tumor was completely resected via a transtemporal approach. The differential diagnosis for these tumors include osteoma, giant cell tumor, histiocytosis, aneurysmal bone cyst and sarcoma. Histologic findings are critical for determining the proper diagnosis.

Recurrent skull base chondrosarcomas (CSA) are difficult to treat, and limited data are available to help guide subsequent therapy.To further characterize the natural history of CSA and identify treatment modalities that were most effective in prolonging progression-free (PFS) and disease-specific survival (DSS).We conducted a single-institution retrospective review of patients with recurrent skull base CSA from 1993 to 2021. Kaplan-Meier survival analyses for PFS and DSS were completed. Univariable and multivariable Cox proportional hazards regression models were used to identify patient-related, treatment-related, and disease-related factors that predicted PFS and DSS.A total of 28 patients and 84 episodes of recurrence were included. One-year PFS was 70.6%, 5-year PFS was 28.9%, and 10-year DSS was 78.5%. The median time to first progression was 23.9 months (range, 2.8-282 months). In univariable Cox proportional hazards regression, male sex, higher grade histology, fourth or greater progression episode status, distal pattern of recurrence, and treatment of recurrence without surgery or with chemotherapy alone predicted worse PFS. Multivariable regression predicted shortened DSS in male patients (hazard ratio [HR] 0.16; P = .021) and higher-grade tumors (HR 0.22; P = .039). Treatment of recurrence with surgery was associated with, but did not significantly predict, improved DSS (HR 1.78; P = .11).Several patient and disease-specific factors were associated with shorter PFS and DSS in recurrent skull base chondrosarcoma. For recurrences amenable to resection, surgery is recommended for treatment of recurrent CSA. Local recurrence management without surgery results in shorter PFS and DSS.

Objective Temporal bone osteoradionecrosis (TBORN) is a rare, chronic complication of head and neck radiation. Initial treatment consists of conservative management, with surgical resection of necrotic bone indicated for cases of severe, symptomatic, or progressive disease. Pentoxifylline-tocopherol (PENTO) has demonstrated usefulness for osteoradionecrosis of other head and neck subsites. Herein, we report five TBORN cases utilizing this protocol. Study design Retrospective case series. Setting Tertiary referral center. Patients This case series describes five TBORN cases in which the PENTO protocol was used in conjunction with conservative management. All patients were women and average age was 61 ± 8 years. Intervention All patients received a daily dose of 800 mg of pentoxifylline and 1 g of tocopherol. Four of the five patients received systemic and/or ototopical antibiotics as an antimicrobial regimen before and/or during the PENTO protocol. Main outcome measures Details regarding the total duration of protocol, improvement in symptoms, exposed bone and radiographic changes, and duration until first improvement of exposed bone were collected retrospectively. Results The average duration of PENTO protocol was 302 ± 166 days. Four of the five (80%) patients demonstrated a decrease in exposed ear canal bone. Three of the five (60%) patients had stable or improvement in otologic symptoms of TBORN. One patient progressed to diffuse TBORN. The average duration until first improvement in exposed bone was 193 ± 137 days. Conclusions The PENTO protocol may be a useful adjunct to conservative measures in the management of localized TBORN. We recommend trialing the protocol for at least 12 months.

Author(s): MD Anderson Head and Neck Surgery Treatment Guidelines Consortium; Consortium members; Maniakas, Anastasios; Jozaghi, Yelda; Zafereo, Mark E; Sturgis, Erich M; Su, Shirley Y; Gillenwater, Ann M; Gidley, Paul W; Lewis, Carol M; Diaz, Eduardo; Goepfert, Ryan P; Kupferman, Michael E; Gross, Neil D; Hessel, Amy C; Pytynia, Kristen B; Nader, Marc-Elie; Wang, Jennifer R; Lango, Miriam N; Kiong, Kimberley L; Guo, Theresa; Zhao, Xiao; Yao, Christopher MKL; Appelbaum, Eric; Alpard, Jennifer; Garcia, Jose A; Terry, Shawn; Flynn, Jill E; Bauer, Sarah; Fournier, Danielle; Burgess, Courtlyn G; Wideman, Cayla; Johnston, Matthew; You, Chenxi; De Luna, Rolando; Joseph, Liza; Diersing, Julia; Prescott, Kaitlin; Heiberger, Katherine; Mugartegui, Lilian; Rodriguez, Jessica; Zendehdel, Sara; Sellers, Justin; Friddell, Rebekah A; Thomas, Ajay; Khanjae, Sonam J; Schwarzlose, Katherine B; Chambers, Mark S; Hofstede, Theresa M; Cardoso, Richard C; Wesson, Ruth Aponte; Won, Alex; Otun, Adegbenga O; Gombos, Dan S; Al-Zubidi, Nagham; Hutcheson, Katherine A; Gunn, G Brandon; Rosenthal, David I; Gillison, Maura L; Ferrarotto, Renata; Weber, Randal S; Hanna, Ehab Y; Myers, Jeffrey N; Lai, Stephen Y | Abstract: BackgroundCOVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel.MethodsThe MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular.RecommendationsEach subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred.ConclusionThese guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

Malignancies involving the temporal bone are increasingly common and require specialized multi-disciplinary care. Given this complex location, involvement of the lateral skull base and local neurovascular structures is common. In this review we discuss general principles for temporal bone resection, as well as alternative and complementary surgical approaches that should be considered in the management of patients with temporal bone cancer. A comprehensive review on literature pertaining to temporal bone resection was performed. The primary surgical strategy for malignancies of the temporal bone is temporal bone resection. This may be limited to the ear canal and tympanic membrane (lateral temporal bone resection) or may include the otic capsule and its contents (subtotal temporal bone resection), and/or the petrous apex (total temporal bone resection). Management of adjacent neurovascular structures including the facial nerve, the carotid artery, and the jugular bulb/sigmoid sinus should be considered during surgical planning. Finally, adjunctive procedures such as parotidectomy and neck dissection may be required based on tumor stage. Temporal bone resection is an important technique in the treatment of lateral skull-base malignancies. This strategy should be incorporated into a multi-disciplinary approach to cancer.

Objectives/hypothesis Examine the presentation and management characteristics of seven patients with melanoma of the external auditory canal (EAC). Study design Retrospective case series and review of the relevant literature. Methods Records of seven patients from 2003 to 2017 with melanoma of the EAC were reviewed for characteristics of presentation, subsequent management, and outcomes. A thorough review of relevant literature is presented. Results The median age is 52 years, with four females. The average Breslow depth was 3.6 mm, with five patients having a Clark level IV or greater on presentation. Six patients underwent lateral temporal bone resection, and one patient underwent wide local excision of the cartilaginous canal. Sentinel lymph node biopsy (SLNB) was performed in three patients. Three patients experienced distant recurrence an average of 20 months following primary therapy. Median follow-up was 21 months. At last follow-up, four were free of disease, one had active disease, and two were deceased from melanoma. Conclusions This is the largest series and the first to report the use of SLNB for patients with EAC melanoma in the peer-reviewed literature. Patients with external auditory canal melanoma present with higher Breslow thickness and stage relative to all external ear melanomas. Management should include wide local excision, which entails lateral temporal bone resection when the bony ear canal is involved. SLNB has a critical role in identifying patients with early metastatic disease. Postoperative radiation therapy should be considered for patients with high-risk features to reduce the risk of locoregional relapse. Chemotherapy, and especially immunotherapy, has an emerging role for this disease. Level of evidence 4 Laryngoscope, 131:165-172, 2021.

Temporal bone squamous cell carcinoma (TBSCC) is rare and often confers a poor prognosis. The aim of this study was to synthesize survival and recurrence outcomes data reported in the literature for patients who underwent temporal bone resection (TBR) for curative management of TBSCC. We considered TBSCC listed as originating from multiple subsites, including the external ear, parotid, and external auditory canal (EAC), or nonspecifically from the temporal bone.PubMed, Cochrane Library, Embase, and manual search of bibliographies.A systematic literature review conducted in December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Survival data were collected from 51 retrospective studies, resulting in a pooled cohort of 501 patients with TBSCC. Compared to patients undergoing lateral TBR (LTBR), patients undergoing subtotal (SBTR) or total (TTBR) TBR exhibited significantly higher rates of stage IV disease (Recurrent disease was associated with risk of death in patients undergoing TBR. Larger prospective multi-institutional studies are needed to ascertain prognostic factors for a wider array of postoperative outcomes, including histology-specific survival and recurrence outcomes.

Synovial sarcomas (SS) are malignant tumors originating from pluripotent mesenchymal cells, with predilection for periarticular areas, as deep-seated soft tissue tumors. Treatment of SS of the head and neck (HN) is usually radical local excision and additional radiation or (neo)adjuvant chemotherapy or both. SS are characterized by a specific SS18-SSX1/2/4 fusion gene. SS have several morphological variants: monophasic, biphasic, or poorly differentiated.We describe a SS of mandibular condyle that showed an overwhelming (95%) epithelial cell component mimicking odontogenic carcinoma. One year prior to presentation, a woman developed a 2.5 cm destructive bone lesion in the left mandibular condyle. The initial diagnosis of ameloblastoma on biopsy was changed to odontogenic carcinoma on the surgical specimen. Four months later a computed tomography (CT) revealed local recurrence; another month later, magnetic resonance imaging (MRI) depicted a new left temporal lobe brain lesion. The patient started on a carboplatin and paclitaxel therapy, with no clinical or radiologic benefit. Subsequently she was presented for another opinion. The pathology material was re-reviewed. Fluorescence in situ hybridization (FISH) resulted a positive result for SS18 (SYT) rearrangement; next generation sequencing (NGS sarcoma fusion panel) reported an SS18-SSX2 fusion transcript. Based on molecular testing the tumor was reclassified as synovial sarcoma. Her systemic treatment was changed to anthracycline based systemic therapy.This case emphasizes the importance of molecular approaches in diagnostic pathology. Accurate diagnosis is imperative to avoid misclassification as carcinoma (metastasis or primary e.g., odontogenic carcinoma), carcinosarcoma or a different sarcoma type with epithelioid or epithelial differentiation and to determine proper treatment.

Emerging immunotherapeutic agents, including immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1), have revolutionized cancer treatment. The first immune checkpoint inhibitor (ICI) ipilimumab, an anti-CTLA-4, was approved in 2011. Since then, the US Food and Drug Administration (FDA) has approved more than half a dozen immune checkpoint inhibitors to treat various malignancies. These agents are part of a broader class of chemotherapy agents termed immunotherapy, which selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. While the effects of traditional chemotherapy are well known, the toxicity profile of emerging immune therapies is not fully elucidated. They have been associated with atypical side effects labeled collectively as immune-related adverse events (irAEs).

Introduction Audiovestibular toxicity secondary to immunotherapy has only rarely been reported in the literature. Herein, we examine our experience diagnosing and managing audiovestibular immune-related adverse events (irAEs) in patients undergoing immunotherapy. Methods Four patients who experienced irAEs were included. Demographics, immunotherapy regimen, diagnostic tests, treatment, and outcomes were recorded in a retrospective chart review. Results The cases of three patients with metastatic melanoma and one patient with metastatic renal cell carcinoma are presented. Hearing loss and tinnitus were the most common presenting symptoms. Immune checkpoint inhibitors (ICIs) were implicated in three cases and T-cell therapy in one case. Two of three patients (67%) treated with steroids had substantial improvements in hearing. Conclusions Audiovestibular irAEs are a rare complication of immunotherapy. Suspicion for symptoms including hearing loss, tinnitus, and/or vertigo should prompt an expedient referral to the otolaryngologist for evaluation, as symptoms may improve with corticosteroid use. Hearing and/or vestibular deficits can have a substantial impact on the quality of life for affected patients, but rehabilitation options do exist.

To review efficiency metrics and patient safety data before and after implementation of a structured review process for surgical innovations.Surgical innovation ranges from minor incremental improvement to radical experimentation. Although innovation paradigms have been described, these are not widely adopted or enforced in the surgical community.A Continuous Quality Improvement Team (CQIT) of surgical quality officers and perioperative nurses was organized to perform structured reviews of proposed new surgical devices and procedures at a large quaternary cancer care center. The CQIT process was placed to precede an established Value Analysis Team business evaluation. Pre- and post-CQIT implementation metrics of approval process efficiency and patient safety data were compared. Seven novel procedures were also vetted by the CQIT.Forty-six product requests were evaluated after CQIT implementation. Compared with 34 products evaluated prior to CQIT establishment, the total mean evaluation time decreased from 124 to 51 days (P= 0.007). For new devices requiring intraoperative trial, the time between product proposal and trial decreased from a mean of 260 to 99 days (P= 0.014). The rate of device-related complications in the pre-CQIT group was 10% compared with 0% post-CQIT. Two devices, which administratively bypassed CQIT review, had both minor and major complications, including a mortality. Five novel procedures approved by CQIT with simulation were performed without complications.Using novel algorithms, the addition of a dedicated team of surgical quality officers to the surgical innovation evaluation process improved both the efficiency and the safety associated with introducing new devices and procedures into practice.

OBJECTIVEThe objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.METHODSFrom 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.RESULTSSeven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.CONCLUSIONSGKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence. Patients and Methods: Newly diagnosed or recurrent stage III–IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response. Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9–54.3] had partial responses by RECIST, 15 patients (75%; 95% CI, 50.9–91.3) had a pCR (n = 11) or MPR (n = 4). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7–26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9–100), 89.5% (95% CI, 76.7–100), and 95% (95% CI, 85.9–100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR. Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.

The middle fossa approach for the resection of small acoustic neuromas is a viable, but underutilized treatment modality with the goal of hearing preservation. The authors aim to demonstrate this approach and its nuances through this video presentation. A 38-year-old man presented with an incidentally discovered small, intracanalicular acoustic neuroma that was initially observed, but growth was noted. The patient had good hearing, and therefore a hearing preservation approach was offered. A gross-total resection was achieved, and the patient maintained good hearing postoperatively. This video demonstrates relevant anatomy, surgical indications, technical aspects of resection, including reconstruction, and postoperative outcomes. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21124

Radiation therapy (RT) to the head and neck (HN) region is critical in the management of various pediatric malignancies; however, it may result in late toxicity. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on salivary dysfunction and dental abnormalities in survivors who received RT to the HN region as children.This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.Of the 2,164 articles identified through a literature search, 40 were included in a qualitative synthesis and 3 were included in a quantitative synthesis. The dose-toxicity data regarding salivary function demonstrate that a mean parotid dose of 35 to 40 Gy is associated with a risk of acute and chronic grade ≥2 xerostomia of approximately 32% and 13% to 32%, respectively, in patients treated with chemo-radiation therapy. This risk increases with parotid dose; however, rates of xerostomia after lower dose exposure have not been reported. Dental developmental abnormalities are common after RT to the oral cavity. Risk factors include higher radiation dose to the developing teeth and younger age at RT.This PENTEC task force considers adoption of salivary gland dose constraints from the adult experience to be a reasonable strategy until more data specific to children become available; thus, we recommend limiting the parotid mean dose to ≤26 Gy. The minimum toxic dose for dental developmental abnormalities is unknown, suggesting that the dose to the teeth should be kept as low as possible particularly in younger patients, with special effort to keep doses20 Gy in patients4 years old.

Objective Endolymphatic sac tumors (ELSTs) are a frequent cause of hearing loss and other audiovestibular dysfunction in patients with von Hippel-Lindau disease (VHL). Unified screening recommendations for VHL patients have not been established. To develop consensus guidelines, the VHL Alliance formed an expert committee to define evidence-based clinical screening recommendations. Patients and Methods Recommendations were formulated by using the Grading of Recommendations, Assessment, Development, and Evaluation framework after a comprehensive literature review. Results Diagnosis of ELSTs in VHL requires a combination of clinical evaluation and imaging and audiometric findings. Audiovestibular signs/symptoms are often an early feature of small ELSTs, including those that are not visible on imaging. Diagnostic audiograms have the greatest sensitivity for the detection of ELST-associated sensorineural hearing loss and can help confirm clinically relevant lesions, including those that may not be radiographically evident. Magnetic resonance imaging (MRI) can be a more specific test for ELSTs in VHL particularly when supplemented with computed tomography imaging for the identification of small tumors. VHL patients between the ages 10 and 60 years carry high preponderance for ELST presentation. Conclusion We recommend that clinical evaluation (yearly) and diagnostic audiograms (every other year) be the primary screening tools for ELSTs in VHL. We suggest that screening be performed between the ages 11 and 65 years or with the onset of audiovestibular signs/symptoms for synchronicity with other testing regimens in VHL. We recommend that baseline imaging (MRI of the internal auditory canals) can be performed between the ages of 15 and 20 years or after positive screening.

Background Skull base osteoradionecrosis (ORN) is a challenging treatment-related complication sometimes seen in patients with cancer. Although ORN management strategies for other anatomic sites have been reported, there is a paucity of data guiding the management of skull base ORN. Objective To report a single-center tertiary care series of skull base ORN and to better understand the factors affecting ORN recurrence after surgical management. Methods We conducted a retrospective cohort study of patients with skull base ORN treated at our center between 2003 and 2017. Univariate and multivariate binary logistic regressions were performed to identify predictors of recurrence. Results A total of 31 patients were included in this study. The median age at ORN diagnosis was 61.1 yr (range, 32.8-84.9 yr). Of these 31 patients, 15 (48.4%) patients were initially treated medically. All 31 patients underwent surgery. Three (14.3%) of 21 patients treated with a free flap and 4 (50.0%) of 8 patients who underwent primary closure experienced recurrence. Cox regression analysis revealed that reconstruction with local tissue closure (P = .044) and ongoing treatment for active primary cancer (P = .022) were significant predictors of recurrence. The median overall survival from index surgery for ORN treatment was 83.9 mo. At 12-mo follow-up, 78.5% of patients were alive. Conclusion In this study, we assess the outcomes of our treatment approach, surgical debridement with vascularized reconstruction, on recurrence-free survival in patients with skull base ORN. Further studies with larger cohorts are needed to assess current treatment paradigms.

Emerging immunotherapy agents, such as immune checkpoint inhibitors, have shown remarkable promise in the treatment of various malignancies. These drugs selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. Due to the novelty of these therapeutic agents, their toxicity profile is less well understood.Meta-analysis results reveal that the overall prevalence of oral mucositis, stomatitis, and xerostomia is lower with checkpoint inhibitors compared to conventional chemotherapy, and head and neck radiation therapy. However, the widespread use of immunotherapy reveals new oral mucosal barrier adverse events, including bullous pemphigoid, mucous membrane pemphigoid, and lichenoid mucositis. Audiovestibular dysfunction can occur from autoimmune-mediated pathways of immunotherapy (adoptive cell) with limited treatment options. Such auditory complications can lead to speech recognition deficits and sensorineural hearing loss. Ocular toxicities are among the most common adverse events resulting from the use of these agents. The majority of ocular immune-related adverse events (irAEs) are mild, low-grade, non-sight threatening, such as blurred vision, conjunctivitis, and ocular surface disease. Serious and sight-threatening events, including corneal perforation, optic neuropathy, and retinal vascular occlusion, can occur but are infrequent. In this chapter, we review the current evidence on the clinical manifestations of oral, audiovestibular, and ocular immune-related adverse events (i.e., irAEs).

Background Skull base chondrosarcomas (CSA) are difficult tumors to cure and there is little data regarding salvage therapy. Objective This study aims to identify presentation and treatment-related factors which impact the progression free survival (PFS) and disease specific survival (DSS) for recurrent CSA, and to identify salvage treatment factors associated with successful restoration to the natural history following primary treatment. Methods This single-institution retrospective review included patients with recurrent/progressive CSA over a 25-year period. Survival analysis for factors impacting PFS and DSS was performed. Salvage treatment factors associated with achieving PFS ≥newly diagnosed median PFS were identified using univariate statistics. Analysis was performed on first recurrences and all recurrences combined. Results A total of 47 recurrence/progression events were analyzed from 17 patients (median two events/patient, range = 1–8). The overall PFS and DSS for the initial recurrence was 32 (range = 3–267) and 79 (range = 3–285) months, respectively. Conventional grade III or mesenchymal histology significantly predicted shorter PFS and DSS (p Conclusion In this series, high grade histology and prior radiation treatment negatively impacted salvage treatment outcomes, while GTR was associated with restoration to natural history following primary treatment. Careful consideration of histology, systemic disease status, previous treatments, and the anatomic extent of the skull base disease can optimize the outcomes of salvage intervention.