Does Time to Initiation of Adjuvant Radiotherapy Affect Reconstruction Outcomes after Endoscopic Resection of Skull Base Malignancies?

Introduction and Objective It is unclear if the length of the time interval to initiation of adjuvant radiation therapy (RT) after endoscopic endonasal surgery affects reconstruction outcomes. In this study we present our experience with adjuvant RT after endoscopic endonasal procedures, to determine if the time to RT after surgery impacts post-RT reconstruction complication rates. Methods A retrospective cohort study of 164 patients who underwent endoscopic endonasal surgery between 1998 and 2021 was conducted. Using Cox proportional hazard ratios (HRs), we evaluated several variables and the complications that occurred during the 1-year period after starting RT. Results Seventy-eight (47.5%) and eighty-six patients (52.5%) received RT before and after the sixth postoperative week, respectively. The overall post-RT complication rates were 28%, most of these were severe infections ( n = 20, 12.2%) and delayed CSF leak ( n = 4, 2.5%). There was no significant difference in the post-RT complications between the patients who received postoperative RT before or after the sixth operative week (HR: 1.13; 95% confidence interval: 0.63-2.02; p = 0.675 ). Univariate analysis demonstrated negative impact associated with smoking history ( p = 0.015 ), the use of neoadjuvant chemotherapy ( p = 0.0001 ), and the use of photon therapy ( p = 0.012 ); and we found a positive impact with the use of multilayer reconstruction techniques (overall, p = 0.041 ; with fat, p = 0.038 ; and/or fascia graft, p = 0.035 ). After a multivariate analysis only, smoking history was an independent risk factor for post-RT complications ( p = 0.012 ). Conclusion Delaying RT for more than 6 weeks after endoscopic endonasal surgery does not provide a significant benefit for reconstruction outcomes. However, special attention may be warranted in patients with smoking history who have received neoadjuvant chemotherapy, or in patients who will receive photon-based RT after surgery as these groups were found to have increased complication rates post-RT.

Impact of Previous Surgery and/or Radiation Therapy on Endoscopic Reconstruction Outcomes.

BACKGROUND AND OBJECTIVES: The impact of prior local therapies, including radiation and surgery, on reconstruction outcomes after endonasal surgery is currently not well known. Reconstruction nuances in the preoperative setting merit further evaluation to avoid potential postoperative complications that can hinder overall tumor management and negatively impact patient outcome. We sought to determine whether prior treatments increase risk of reconstruction-related postoperative morbidity and to evaluate the effectiveness of our current treatment paradigm for skull base reconstruction. METHODS: A retrospective review of all endonasal surgeries for tumor resection between March 2000 and March 2022 was performed. Patients were grouped based on treatment history. Patient demographics, operative, and postoperative reconstruction-related morbidity data were collected, including cerebrospinal fluid leak, sinonasal morbidity, and infectious complications. Variables significantly associated with postoperative complications in the univariate analysis were included in the multivariate Cox proportional hazards regression model. Complication-free survival curves were generated, and the log-rank test evaluated the relationship between complication-free survival and the different clinical, surgical, and treatment parameters. All statistical analyses were performed with SPSS 26 (IBM Corp) and Graph Pad 9.0 (GraphPad Software). RESULTS: A total of 418 patients were included. 291 patients had no prior treatments, 49 patients had previously received radiation, and 78 patients had prior surgeries. Of the 49 patients who had prior radiation, 27% underwent reconstruction with tunneled pericranial flaps vs 16% of treatment-naïve patients. On multivariate analysis, prior treatment was not significantly associated with reconstruction-related complications. Negative smoking history, no leak or small intraoperative leak, and use of vascularized flap in reconstruction were protective factors. CONCLUSION: In patients undergoing endonasal surgery, prior radiation and/or surgery does not appear to significantly increase the risk of immediate or delayed reconstruction complications using our current reconstructive management plan, which incorporates an upfront regional flap for high-risk cases.

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Targeting sinonasal undifferentiated carcinoma with a combinatory immunotherapy approach.

PURPOSE: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of the sinonasal cavity with poor prognosis and limited treatment options. To investigate the potential for SNUC sensitivity to combinatory immunotherapy, we performed in vitro studies with SNUC cell lines and used multi-spectral immunofluorescence to characterize the in vivo patient SNUC tumor immune microenvironment (TIME). EXPERIMENTAL DESIGN: Human-derived SNUC cell lines were used for in vitro studies of tumor cell susceptibility to natural killer (NK) cell-based immunotherapeutic strategies. Tumor samples from 14 treatment naïve SNUC patients were examined via multi-spectral immunofluorescence and clinical correlations assessed. RESULTS: Anti-PD-L1 blockade enhanced NK cell lysis of SNUC cell lines ∼5.4 fold (P ≤ 0.0001). This effect was blocked by a CD16 neutralizing antibody demonstrating activity through an antibody-dependent cellular cytotoxicity (ADCC) mediated pathway. ADCC-dependent lysis of SNUC cells was further enhanced by upregulation of PD-L1 on tumor cells by exogenous interferon-gamma (IFN-γ) administration or interleukin-15 (IL-15) stimulated IFN-γ release from NK cells. Combination treatment with anti-PD-L1 blockade and IL-15 superagonism enhanced NK-cell killing of SNUC cells 9.6-fold (P ≤ 0.0001). Untreated SNUC patient tumor samples were found to have an NK cell infiltrate and PD-L1+ tumor cells at a median of 5.4 cells per mm2. A striking 55.7-fold increase in CKlow tumor cell/NK cell interactions was observed in patients without disease recurrence after treatment (P = 0.022). Patients with higher CD3+CD8+ in the stroma had a significantly improved 5-year overall survival (P = 0.0029) and a significant increase in CKlow tumor cell/CD8+ cytotoxic T cell interactions was noted in long-term survivors (P = 0.0225). CONCLUSION: These data provide the pre-clinical rationale for ongoing investigation into combinatory immunotherapy approaches for SNUC.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Intestinal-Type Adenocarcinoma in Head and Neck: Dissecting Oncogenic Gene Alterations Through Whole Transcriptome and Exome Analysis.

Adenocarcinomas of the nasal/paranasal sinuses are uncommon, but intestinal-type adenocarcinomas (ITACs) are important. Due to the rarity of these tumors, their molecular profile is not well known. To further investigate the molecular profile and find potential oncogenic drivers, we compared the whole transcriptome and exome of ITACs at different anatomic locations in the head and neck. Twenty-one head and neck adenocarcinomas were used in this study, divided into 10 sinonasal adenocarcinomas (SNT) and 11 extrasinonasal (T) head and neck adenocarcinomas according to anatomic location and histology. Tumor samples along with normal mucosa were microdissected from formalin-fixed, paraffin-embedded samples, and RNA and DNA were subjected to whole-transcriptome and -exome shotgun sequencing. Analysis of ITACs at sinonasal locations showed 410 subtype-specific differentially expressed (DE) genes and noncoding transcripts compared with the group of other anatomic locations, with 2909 subtype-specific DE genes. The groups shared 872 genes, with 17 highly different or opposing DE genes. Whole-exome mutation analysis revealed the gene MLL3 (KMT2C) to be exhibiting the most frequent loss-of-function mutations in all adenocarcinomas investigated. The results suggest that the head and neck ITACs investigated were mainly caused by loss-of-function mutations in MLL3 that disabled chromatin methylation and remodeling of all MLL3-targeted enhancers in the tumors. This changed the activity of multiple genes/gene clusters, supporting oncogenicity mostly via pathways of signaling, dedifferentiation, proliferation, migration, and immune and inflammatory deregulation, indicating a truly epigenetic event as the root cause for the heterogenous diversity of these enteric types of cancer. The data of this study form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites and show the contribution of different mucosal components to the etiology/molecular pathology of ITAC.

Long-term oncological outcomes for endoscopic endonasal versus open surgical approaches for anatomically matched, locally advanced stage T4 sinonasal malignancies with skull base involvement.

OBJECTIVE: Expanded endoscopic approaches (EEAs) are increasingly used for the definitive management of sinonasal malignancies. EEAs, in appropriately selected cases, provide similar oncological outcomes but are associated with lower complication rates compared with open surgical approaches. Selection bias is a limitation reported in previous studies comparing EEAs and open surgical approaches for the management of sinonasal malignancies. To address this issue, in this study the authors compared the long-term oncological outcomes of an anatomically matched cohort of patients with locally advanced sinonasal malignancies with skull base involvement (T4 stage). The specific objective of this study was to investigate the extent of resection (EOR), overall survival (OS), and disease progression between the EEA and open surgical cohorts. METHODS: A cohort of 42 patients with locally advanced sinonasal malignancies and skull base involvement (stage T4) and operated on via an EEA was matched anatomically with a cohort of 54 patients who had undergone open surgery. A retrospective chart review was conducted on these 96 patients who were treated between September 1993 and June 2020. All patients in the cohort were eligible for either an EEA or open surgery according to anatomical criteria. Patients of all ages were included, and the minimum follow-up required for eligibility was 4 months. Patients were excluded if surgery was not offered for curative intent and preoperative imaging did not demonstrate that gross-total resection was achievable. RESULTS: There were more complications in the conventional surgery cohort than in the EEA cohort (33.33% vs 14.29%, p = 0.033). There was no significant difference in the EOR between the EEA and conventional surgery cohorts, as demonstrated by comparable rates of positive margins in both groups (5.56% vs 2.38%, respectively). Disease progression (hazard ratio [HR] 0.47, 95% CI 0.17-1.27, p = 0.137) was lower and OS (HR 0.58, 95% CI 0.26-1.29, p = 0.183) was higher in the EEA cohort, but these findings did not reach statistical significance. CONCLUSIONS: The EEA was found to be associated with lower risks of complications than conventional craniofacial surgical approaches. There were no significant differences in OS and progression-free survival between the EEA and conventional surgical cohorts when comparing anatomically matched cohorts of patients with stage T4 sinonasal malignancies and skull base involvement.

Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance.

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

Sinonasal NUT carcinoma: A consecutive case series and systematic review.

BACKGROUND: Sinonasal NUT carcinoma is an extremely rare, lethal malignancy with limited literature. METHODS: A case series was conduction of all patients with sinonasal NUT carcinoma at a single institution between 2010 and 2022. Survival and associated were evaluated. A systematic review of the literature was performed. RESULTS: In 12 patients, followed for a median of 1.5 years, the median overall survival (OS) and disease-specific survival (DSS) were both 14.6 months. Patients with maxillary sinus tumors were 91% more likely to survive (hazard ratio [HR]: 0.094, 95% confidence interval [CI]: 0.011-0.78, p = 0.011). Patients with higher-stage disease stage had worse OS (stage IVb-c vs. III-IVa, p = 0.05). All three patients who were alive with no evidence of disease received induction chemotherapy. CONCLUSION: For patients with sinonasal NUT carcinoma, the median survival was 15 months but better with lower-stage and maxillary tumors. Induction chemotherapy may be beneficial.

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant. METHODS: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables. RESULTS: A total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5-30 months) comprised our study cohort. Overall, 25.7% of patients had pre-existing CVD prior to ICI treatment. Of the remaining 453 patients without pre-existing CVD, 31.5% (n = 143) had at least one CVD-related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD-related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5-6.8 months), followed by myocardial infarction (3.7, 0.5-9), cardiomyopathy (4.5, 1.6-7.3), and tachyarrhythmias (4.9, 1.2-11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care. CONCLUSION: The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI-induced cardiovascular toxicities is yet to be fully defined in HNC survivors.

Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA).

Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients. Clinical trials, while promising, have been difficult to activate and accrue. While individual institutions and investigators have attempted to seek solutions to such problems, international, national, and local partnership may provide the keys to more efficient and innovative paths forward. Furthermore, a mucosal melanoma coalition would provide a potential network for patients and caregivers to seek expert opinion and advice. The Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA) highlighted the current clinical challenges faced by patients, providers, and scientists, identified current and future clinical trial investigations in this rare disease space, and aimed to increase national and international collaboration among the mucosal melanoma community in an effort to improve patient outcomes. The included proceedings highlight the clinical challenges of mucosal melanoma, global clinical trial experience, basic science advances in mucosal melanoma, and future directions, including the creation of shared rare tumor registries and enhanced collaborations.

Prevalence of pituitary hormone dysfunction following radiotherapy for sinonasal and nasopharyngeal malignancies.

BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation. METHODS: Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated. RESULTS: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P = 0.04), pituitary stalk (1129 cGy, P = 0.02), optic chiasm (1094 cGy, P = 0.01), and hypothalamus (900 cGy, P = 0.01). CONCLUSIONS: Nearly half of the patients had abnormal pituitary function, including over a tenth requiring treatment. There may be a dose-dependent association between hormonal dysfunction and radiation.

Predictors of postoperative performance status after surgical management of infratemporal fossa malignancies.

Infratemporal fossa (ITF) tumors are difficult to access surgically due to anatomical constraints. Moreover, aggressive ITF carcinomas and sarcomas necessitate aggressive treatment strategies that, along with tumor-related symptoms, contribute to decreases in patient performance status. To assess factors that predict postoperative performance in patients undergoing surgery for ITF tumors. We reviewed medical records for all patients surgically treated for an ITF malignancy between January 1, 1999, and December 31, 2017, at our institution. We collected patient demographics, preoperative performance, tumor stage, tumor characteristics, treatment modalities, pathological data, and postoperative performance data. The 5-year survival rate was 62.2%. Higher preoperative Karnofsky Performance Status (KPS) score (n = 64; p < 0.001), short length of stay (p = 0.002), prior surgery at site (n = 61; p = 0.0164), and diagnosis of sarcoma (n = 62; p = 0.0398) were predictors of higher postoperative KPS scores. Percutaneous endoscopic gastrostomy (PEG) (n = 9; p = 0.0327), and tracheostomy tube placement (n = 20; p = 0.0436) were predictors of lower postoperative KPS scores, whereas age at presentation (p = 0.72), intracranial tumor spread (p = 0.8197), and perineural invasion (n = 40; p = 0.2195) were not. Male patients and patients with carcinomas showed the greatest decreases in KPS scores between pretreatment and posttreatment. Higher preoperative KPS score and short length of stay were the best predictors of higher postoperative KPS scores. This work provides treatment teams and patients with better information on outcomes for shared decision-making.

Impact of Clinical Factors and Treatments on SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma.

The objective of this study was to report outcomes for 19 consecutive patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma. Patients were treated from 2014 to 2021 and followed for a median of 22.3 months. The median overall survival (OS) and disease-free survival (DFS) were 31.8 and 9.9 months, respectively. Patients with nasal cavity or maxillary sinus tumors had 84% better disease-specific survival (DSS) (hazard ratio [HR], 0.136; 95% confidence interval [CI], 0.028-0.66; p = .005) and 71% better DFS (HR, 0.29; 95% CI, 0.097-0.84; p = .041) than patients with other sinonasal sites. Patients who received induction chemotherapy were 76% less likely to die of disease (DSS HR, 0.241; 95% CI, 0.058-1.00; p = .047). In the largest single-institution study of SMARCB1-deficient sinonasal carcinoma to date, OS and DFS approached 3 years and 1 year, respectively, but were better for nasal cavity and maxillary sinus tumors. Patients may benefit from induction chemotherapy.

Modern treatment of sinonasal undifferentiated carcinoma.

PURPOSE OF REVIEW: Sinonasal undifferentiated carcinomas are rare aggressive tumours with traditionally poor outcomes. Although multimodality treatment has been recommended by most centres, the ideal treatment sequence or regimen has not been established. RECENT FINDINGS: Recent evidence suggests that induction chemotherapy may be used for chemoselection and cytoreduction prior to definitive chemoradiotherapy. Where there is a favourable response, concurrent chemoradiotherapy is favoured, with an improved overall survival and improved rates of organ preservation. SUMMARY: Induction chemotherapy may be a useful guide for selection of patients for chemoradiotherapy or surgery and has shown encouraging results. Further research is required to establish the ideal induction chemotherapy regimen for this rare group of tumours.

Association of hearing loss and tinnitus symptoms with health-related quality of life among long-term oropharyngeal cancer survivors.

BACKGROUND: 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. METHODS: 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 Head & Neck 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. RESULTS: 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. CONCLUSIONS: 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.

Olfactory Neuroblastoma: Morphological Reappraisal and Molecular Insights with Quantum Leap in Clinical Perspectives.

PURPOSE OF REVIEW: The purpose of review is to provide a comprehensive review of the literature focusing on the recent advances in the diagnosis, molecular underpinning, and targeted therapy of olfactory neuroblastoma (ONB). RECENT FINDINGS: Studies focused on the molecular fingerprinting of ONB are critical to engage new promising treatment strategies. Molecular-based subtype classifications have been proposed (basal-like ONB and neural-like ONB) but are not widely used. The rationale for implementation of DNA methylation analysis and IDH2 sequencing in routine work-up for ONB is gaining recognition. Expression of somatostatin receptors (SSTR) in ONB open new avenues for both, diagnostic (especially metastatic disease) and new treatment protocols with somatostatin analogs. Olfactory carcinoma is proposed as a unifying diagnostic terminology pertinent to epithelial divergent differentiation in olfactory neuroblastoma. Molecular (genetic and epigenetic) efforts on olfactory neuroblastoma are promising; however further refinement is needed for employment of these biomarkers as clinical standard of care. Ongoing and future multi-institutional collaborative studies will contribute to further understanding of ONB biology and aid the development of targeted treatments for this disease.

The combined profunda artery perforator-gracilis flap for immediate facial reanimation and resurfacing of the radical parotidectomy defect.

BACKGROUND: A radical parotidectomy with facial nerve sacrifice results in facial nerve paralysis as well as a volume and often cutaneous defect. Prior experience with nerve grafting and static suspension has yielded suboptimal results. The present report aims to examine the feasibility and outcomes of a combined free gracilis and profunda artery perforator (PAP) flap from a single donor site can reconstruct these extensive defects and potentially restore dynamic facial reanimation even in the setting of adjuvant radiation. PATIENTS AND METHODS: A retrospective review of 10 patients (6 males and 4 females) was performed from 2016 to 2020 that underwent a combined PAP-gracilis reconstruction of a radical parotidectomy defect. All patients (mean age: 71.3 years; range: 52-83 years) received adjuvant radiation. A chimeric PAP-gracilis flap requiring a single microvascular anastomosis was performed in three patients while the remaining patients underwent a double free flap reconstruction. RESULTS: The gracilis flap was innervated using the facial nerve stump, spinal accessory and massecteric nerve in three patients each. One patient's gracilis was innervated using the hypoglossal nerve. Three patients also underwent nerve grafting of the facial nerve. One patient was taken back to the operating room for a hematoma in the recipient site and there were not flap losses of either the PAP or gracilis flap. Two patients had delayed wound healing of the donor site that healed with conservative management. Average follow-up was 11.1 months (range: 8.1-19.5 months). Six patients were able to achieve dynamic animation while the others obtained a static reconstruction and did not have issues with drooling, eating, or speaking. CONCLUSIONS: Immediate functional muscle transfer can potentially restore dynamic facial reanimation even following radiation. Combining reconstruction using a PAP-gracilis flap addresses the soft tissue deficit and facial paralysis using a single donor site in a single operation.