Survival Outcomes of Temporal Bone Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Temporal bone squamous cell carcinoma (TBSCC) is a rare malignancy with poor prognosis, and optimal treatment for advanced cases is uncertain. Our systematic literature review aimed to assess 5-year survival outcomes for advanced TBSCC across different treatment modalities. DATA SOURCES: EMBASE, Medline, PubMed, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for articles published between January 1989 and June 2023. RESULTS: The review yielded 1229 citations of which 31 provided 5-year survival data for TBSCC. The final analysis included 1289 patients. T classification data was available for 1269 patients and overall stage for 1033 patients. Data for 5-year overall survival (OS) was 59.6%. Five-year OS was 81.9% for T1/2 and 47.5% for T3/4 (P < .0001). OS for T1/T2 cancers did not significantly differ between surgery and radiation (100% vs 81.3%, P = .103). For advanced-stage disease (T3/T4), there was no statistical difference in OS when comparing surgery with postoperative chemoradiotherapy (CRT) (OS 50.0%) versus surgery with postoperative radiotherapy (XRT) (OS 53.3%) versus definitive CRT (OS 58.1%, P = .767-1.000). There was not enough data to assess the role of neoadjuvant CRT. CONCLUSION: Most patients will present with advanced-stage disease, and nodal metastasis is seen in nearly 22% of patients. This study confirms the prognostic correlation of the current T classification system. Our results suggest that OS did not differ significantly between surgery and XRT for early stage disease, and combined treatment modalities yield similar 5-year OS for advanced cancers.

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.

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.

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.

Survival Outcomes of Patients with Mycosis Fungoides Involving the External Ear and Ear Canal.

OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: Retrospective analysis. METHODS: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021. RESULTS: 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). CONCLUSIONS: 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 OF EVIDENCE: 4 Laryngoscope, 133:1486-1491, 2023.

Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma.

OBJECTIVES: Map regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence. MATERIALS AND METHODS: Retrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997-2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression. RESULTS: Regional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2-3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9-9.3; T4 vs. T1: HR 2.3, 95% CI 1.2-4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2-16.1), upper alveolus (HR 3.2, 95% CI 1.0-4.7) or with LVI (HR 2.0, 95% CI 1.0-3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases. CONCLUSIONS: For lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3-4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.

Outcomes after definitive surgery for mandibular osteoradionecrosis.

OBJECTIVES: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN). MATERIALS AND METHODS: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009. RESULTS: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94). CONCLUSIONS: Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors.

Perineural Invasion of the Intratemporal Facial Nerve: How Far Proximally Do We Chase the Positive Margin?

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.

Neoadjuvant chemotherapy for locoregionally advanced squamous cell carcinoma of the paranasal sinuses.

BACKGROUND: Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. METHODS: The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. RESULTS: The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). CONCLUSIONS: The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

Endoscopic resection of sinonasal malignancies.

BACKGROUND: In this study, we evaluate our experience and the outcomes of patients with sinonasal cancer treated with endoscopic resection. METHODS: Retrospective review of patients with sinonasal cancer who had endoscopic resection was conducted. The outcomes of interest included survival outcomes and surgical complications. RESULTS: Overall, 239 patients were included. Median follow up time was 46.6 months. Of the 239 patients, 167 (70%) had a pure endonasal endoscopic approach, while 72 (30%) had an endoscopic-assisted approach. Postoperative cerebrospinal fluid (CSF) leakage occurred in 14 patients (5.9%). Negative margins were achieved in 209 patients (87.4%). There was no significant difference in the margin status between the pure endoscopic and endoscopic-assisted group (P = .682). There was no significant difference in the survival outcomes between both the groups. CONCLUSION: Our data suggest that in properly selected patients, endoscopic approaches have acceptable morbidity with low complication rates and can provide an oncologically sound alterative to open approaches.

Identification of markers predictive for response to induction chemotherapy in patients with sinonasal undifferentiated carcinoma.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Despite aggressive multimodal therapy, its prognosis remains poor. Because of its locally advanced nature and high propensity for distant metastasis, we frequently use induction chemotherapy before definitive therapy in patients with SNUC. However, about 30% of patients do not respond to induction chemotherapy, and lack of response is associated with a poor survival rate. Therefore, in this study, we performed gene expression analysis of SNUC samples to identify prognostic markers for induction chemotherapy response. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded SNUC tumor samples from previously untreated patients harvested before induction chemotherapy were used. Gene expression was performed using an oncology gene expression panel. RESULTS: We identified 34 differentially expressed genes that distinguish the responders from the non-responders. Pathway analysis using these genes revealed alteration of multiple pathways between the two groups. Of these 34 genes, 24 distinguished between these two groups. Additionally, 16 gene pairs were associated with response to induction therapy. CONCLUSION: We identified genes predictive of SNUC response to induction chemotherapy and pathways potentially associated with treatment outcome. This is the first report of identification of predictive biomarkers for response of SNUC to induction chemotherapy, and it may help us develop therapeutic strategies to improve the treatment outcomes of non-responders.

Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. It is often difficult to determine whether SNUC is a distinct pathologic entity with poorly differentiated neuroendocrine features or it represents an undifferentiated tumor of squamous lineage. Also, reliable histopathologic markers that distinguish SNUC from poorly differentiated sinonasal squamous cell carcinoma (SNSCC) are lacking. Therefore, identification of new diagnostic molecular markers for SNUC is needed. METHODS: Treatment-naïve tumor specimens obtained from 15 SNUC and 6 SNSCC patients were used. Gene expression analysis was performed using an oncology panel. RESULTS: An unsupervised cluster analysis divided the patients into the one with only SNUCs and the one with mainly SNSCCs. Of 132 differentially expressed genes, 7 genes completely distinguished SNUCs from SNSCCs. SNUCs were enriched in sets of genes related to DNA repair, synthesis/replication, and cell division. CONCLUSIONS: Our study identified new diagnostic markers and potential therapeutic targets for SNUC.

PD-L1 expression by immunohistochemistry in salivary duct carcinoma.

BACKGROUND: Immune checkpoint inhibitors play an increasing role in oncologic care. PD-L1 expression is associated with survival and predicts response to PD-1 or PD-L1 inhibitors in a variety of tumors. Our aim is to evaluate the frequency and prognostic significance of PD-L1 expression in salivary duct carcinoma. DESIGN: We retrospectively evaluated the expression of PD-L1 by two different antibodies (PD-L1 28-8 and PD-L1 22C3) in salivary duct carcinomas. PD-L1 expression in at least 1% of tumor cells was considered immunoreactive. Kaplan-Meier analysis was performed to determine the impact of PD-L1 expression on survival; differences between survival curves were assessed by the chi-square test, and pairwise comparisons of factors were assessed with the log-rank test. RESULTS: A total of 113 patients' specimens were evaluated. Seventy-six (76%) of the patients were male. Mean age at time of presentation was 61.2 (SD = 12.4) years. PD-L1 expression was found in 26% of the samples. Median follow-up time was 36.6 months (range = 1.4-249 months). Overall survival at 3, 5 and 10 years were 52.6%, 37.9% and 25.6%, respectively. There was no statistical difference in survival between patients with PD-L1-immunoreactive tumors and those without, regardless of which antibody was used (chi2 result for all plots: p = 0.53; log rank test for pairwise comparison: p > 0.256). CONCLUSION: In our analysis, PD-L1 expression occurred in a small proportion of salivary duct carcinomas, usually at low levels, and did not correlate with survival. Its predictive value and utility in selecting patients with salivary duct carcinoma who might benefit from PD-1/PD-L1 inhibitors warrants further investigation.

Evaluating Perineural Spread to the Intratemporal Facial Nerve on Magnetic Resonance Imaging.

OBJECTIVES: To determine the sensitivity and specificity of magnetic resonance imaging (MRI) for the detection of perineural spread (PNS) along the intratemporal facial nerve (ITFN) in patients with head and neck cancers. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: We included 58 patients with head and neck malignancies who underwent sacrifice of the ITFN between August 1, 2002, and November 30, 2015. Demographics, preoperative facial nerve function, prior oncologic treatment, and timing between MRI and surgery were recorded. Histopathology slides and preoperative MRI were reviewed retrospectively by a neuropathologist and a neuroradiologist, respectively, both blinded to clinical data. The mastoid segment of the facial nerve (referred to as the descending facial nerve [DFN]) and stylomastoid foramen (SMF) were evaluated separately. A grading system was devised when radiographically assessing PNS along the DFN. RESULTS: Histopathologic evidence of PNS was found in 21 patients (36.2%). The sensitivity and specificity of MRI in detecting PNS to the DFN were 72.7% and 87.8%, respectively. MRI showed higher sensitivity but slightly lower specificity when evaluating the SMF (80% and 82.8%, respectively). Prior oncologic treatment did not affect the false-positive rate ( P = .7084). Sensitivity was 100% when MRI was performed within 2 weeks of surgery and was 62.5% to 73.3% when the interval was greater than 2 weeks. This finding was not statistically significant (SMF, P = .7076; DFN, P = .4143). CONCLUSION: MRI shows fair to good sensitivity and good specificity when evaluating PNS to the ITFN.

Induction Chemotherapy Response as a Guide for Treatment Optimization in Sinonasal Undifferentiated Carcinoma.

PURPOSE: Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC. METHODS: Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation. RESULTS: A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]). CONCLUSION: In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity.

BACKGROUND: Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined. METHODS: We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center. RESULTS: One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow-up time was 55 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10-year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival. CONCLUSION: In this large cohort of patients with sinonasal ACC with extended follow-up, long-term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy.

BACKGROUND: Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small-molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known about the role and clinical implications of alterations of the HER2/PI3K pathway in patients with SDC. METHODS: The authors investigated the clinicopathologic features, genetic alterations, and expression of key members of the HER2/PI3K pathway in 43 primary tumors and conducted in vitro functional and targeted drug-response analyses on cell lines derived from salivary epithelial carcinomas. RESULTS: In primary tumors, loss of phosphatase and tensin homolog (PTEN) expression was identified in 22 of 43 tumors (51%), overexpression of HER2 was observed in 12 of 43 tumors (28%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations were identified in 12 of 43 tumors (28%). Phosphorylated protein kinase B (p-AKT) was highly expressed in most tumors. Most tumors (70%) displayed mutually exclusive alterations of PI3K members, whereas 8 tumors (19%) had 2 or more concurrent abnormalities. In vitro studies demonstrated a direct association between PTEN loss and PI3K pathway activation and evidence of response to combined PI3Kα and PI3Kß and/or pan-PI3K inhibitors. CONCLUSIONS: The current analyses reveal frequent PTEN loss and mutually exclusive alterations of key PI3K pathway members in SDC and demonstrate in vitro evidence of a response to pan-PI3K inhibitors. These results provide a framework for a biomarker-based substratification of patients with SDC in future targeted therapy. Cancer 2018;124:3523-32. © 2018 American Cancer Society.

Approaches to regional lymph node metastasis in patients with head and neck mucosal melanoma.

BACKGROUND: Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival. METHODS: The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes. RESULTS: Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]). CONCLUSIONS: The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Early Stage olfactory neuroblastoma and the impact of resecting dura and olfactory bulb.

OBJECTIVE: Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. METHODS: Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. RESULTS: Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. CONCLUSION: Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1274-1280, 2018.