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Background: Endoscopic endonasal skull base surgery has become a viable alternative to open procedures for the surgical treatment of benign and malignant lesions in the sinonasal and skull base regions. As in sinus surgery, skull base surgery may cause crusting and posterior rhinorrhea, particularly when a nasoseptal flap is required for skull base reconstruction. Post-operative radiological sinonasal findings have been reported previously with no clear correlation with intraoperative decision-making. As in open surgery, endoscopic surgery is not standardized and there is variability in the intervention to assist with exposure and skull base repair. These modifications, including middle turbinate resection, nasoseptal flap, fat graft, and maxillary antrostomy have the potential for nasal morbidity. The aim of this study was to evaluate whether specific interventions during surgery or specific patient and tumor characteristics harbor a more significant risk of causing nasal morbidity post-operatively, as demonstrated by post-operative imaging. Methods: A retrospective analysis of all patients who underwent endoscopic endonasal skull base surgery for pituitary lesions at two major referral centers was performed. Data on demographic, clinical, and pathological features were collected, and pre- and post-operative imaging studies (computed tomography (CT) and magnetic resonance imaging (MRI)) were reviewed and scored according to the Lund–Mackay (LM) scoring system. Results: The study included 183 patients. Radiographic evidence of sinusitis was observed in 30 patients (LM score > 4) in post-operative imaging studies. Patients who underwent middle turbinectomy or nasoseptal flap were found to have significantly higher LM scores on follow-up imaging. A nasoseptal flap was found to be associated with an average increase in LM score of 1.67 points and middle turbinectomy with an average increase of 2.21 points. There was no correlation between tumor size and findings that were compatible with sinusitis on post-operative imaging. Conclusions: The findings of the present study suggest that endoscopic endonasal skull base surgery is associated with radiological evidence of sinusitis. Nasoseptal flap reconstruction and middle turbinectomy were strongly associated with radiographic sinusitis and should be judiciously performed during surgery. A clinical correlation is needed for further recommendations. [ABSTRACT FROM AUTHOR]

Despite great promise, combining anti-angiogenic and conventional anti-cancer drugs has produced limited therapeutic benefit in clinical trials, presumably because mechanisms of anti-angiogenic tissue response remain only partially understood. Here we define a new paradigm, in which anti-angiogenic drugs can be used to chemosensitize tumors by targeting the endothelial acid sphingomyelinase (ASMase) signal transduction pathway. We demonstrate that paclitaxel and etoposide, but not cisplatin, confer ASMase-mediated endothelial injury within minutes. This rapid reaction is required for human HCT-116 colon cancer xenograft complete response and growth delay. Whereas VEGF inhibits ASMase, anti-VEGFR2 antibodies de-repress ASMase, enhancing endothelial apoptosis and drug-induced tumor response in asmase+/+, but not in asmase-/-, hosts. Such chemosensitization occurs only if the anti-angiogenic drug is delivered 1-2h before chemotherapy, but at no other time prior to or post chemotherapy. Our studies suggest that precisely-timed administration of anti-angiogenic drugs in combination with ASMase-targeting anti-cancer drugs is likely to optimize anti-tumor effects of systemic chemotherapy. This strategy warrants evaluation in future clinical trials.

Simple Summary: While the initial favorable efficacy and safety profile for a novel diffusing alpha-emitter radiation therapy (Alpha DaRT) have been previously demonstrated, the longer-term safety and durability of the treatment are unknown. In this pooled analysis of 81 treated head and neck or skin tumors from four clinical trials with a median follow-up of 14 months, a complete response was observed in 89% of treated lesions, two-year local recurrence-free survival was 77%, and there were no grade 2 or higher late toxicities observed. These results suggest that Alpha DaRT is a safe and effective treatment for skin and head and neck tumors. The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2–51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63–87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial. [ABSTRACT FROM AUTHOR]

Objectives: Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. Methods: A retrospective analysis of all surgically treated patients with OSCC at a university‐affiliated tertiary care center between 2000 and 2020. Results: Two hundred seventy‐nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non‐OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease‐free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5‐year DFS (34.7% vs. 61.3%, log‐rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9–19). Conclusions: OSCC patients with OLP background demand close clinical follow‐up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. Level of Evidence: 3 Laryngoscope, 134:3146–3151, 2024 [ABSTRACT FROM AUTHOR]

Background: Regional metastases are considered the most important prognostic factor in OSCC patients. We aimed to investigate the impact of regional disease among different age groups with OSCC. Methods: A retrospective comparison between patients 40 years old or younger, 41–69 years old, and 70 years or older treated for OSCC between 2000 and 2020 in a tertiary‐care center. Results: 279 patients were included. The mean age was 65 ± 17.7 and 133 were male (47.7%). Thirty‐six (12.9%) were 40 years old or younger, 101 (36.2%) were 41–69 years and 142 (50.9%) were 70 years or older. Five‐year overall survival and disease‐specific survival (DSS) were significantly better among patients younger than 40 compared to the mid‐age group and patients 70 years or older (76.7% vs. 69.4% vs.48.2%, Log‐rank p < 0.001, and 76.7% vs. 75.3% vs. 46.5%, Log‐rank p < 0.001, respectively). While an association between regional spread and overall survival and DSS was demonstrated among all age groups, the odds ratio (OR) for death of any cause and death of disease regarding cervical metastasis was much higher among patients younger than 40 compared with the 41–69 and 70+ age groups (death of any cause‐OR = 23, p‐value = 0.008, OR = 2.6, p‐value = 0.026, OR = 2.4, p‐value = 0.13, respectively. Death of disease‐OR = 23, p‐value = 0.008, OR = 2.3, p‐value = 0.082, OR = 4.1, p‐value = 0.001, respectively). In univariate analysis, regional metastasis was associated with disease‐free survival only among patients younger than 40 (p‐value = 0.04). Conclusions: Regional metastases correspond with worse prognosis in young patients compared to older patients. These patients may benefit from a comprehensive treatment approach with close post‐treatment follow‐up. Level of Evidence: 3 Laryngoscope, 134:2212–2220, 2024 [ABSTRACT FROM AUTHOR]

Objectives: Secretory Carcinoma is a malignant salivary gland tumor, initially described in 2010. This rare tumor is associated with the translocation t(12;15) (p13;q25), resulting in the fusion gene ETV6‐NTRK3. Since this tumor is quite rare, most publications describe only small cohorts of patients. We aimed to investigate the clinical, pathological, and prognostic features of this newly defined malignant entity. Data Sources: Pubmed, Google Scholar, and Web of Science databases. Review Methods: All published articles between 2010 and 2023 were reviewed. Search terms included the terms "Mammary Analogue Secretory Carcinoma" and "Secretory Carcinoma". All articles published in English reporting on Secretory Carcinoma of salivary glands were retrieved. Results: One‐hundred and 12 retrospective articles reporting a total of 674 patients were included, with 52% males and a mean age of 44.9 ± 18.9. The event rate for patients with advanced‐stage disease (Stage 3/4) at presentation was 24.1% (95% CI 17.6%–31.9%, I2 = 9.2%), 14.6% for regional metastases (95% CI 10.5%–20%, I2 = 12%), and the event rate of distant metastasis was 8.4% (95% CI 5.5%–12.7%, I2 = 4.2%). Adjuvant radiotherapy was administered for 30.3% of patients (95% CI 24.1%–37.2%, I2 = 21.5%). The recurrence rate was 19% (95% CI 15.1%–23.8%, I2 = 5%). Survival outcomes showed a 17.2% death of disease rate for Secretory Carcinoma patients (95% CI 13.5%–21.8%, I2 = 7.3%). Conclusions: Secretory Carcinoma is a rare and relatively newly defined entity arising in the parotid gland most commonly. Characterized as a low‐grade tumor, the majority of patients are diagnosed at an early stage, without regional or distant disease, and the prognosis is relatively good. Level of Evidence: NA Laryngoscope, 134:1716–1724, 2024 [ABSTRACT FROM AUTHOR]

Background: While almost one-third of patients treated for laryngeal cancer will experience disease recurrence, the current National Comprehensive Cancer Network guidelines do not recommend routine post-treatment imaging follow-up. We aimed to examine the yield of post-treatment imaging surveillance among patients with primary advanced laryngeal cancer. Methods: Patients treated for advanced-stage laryngeal carcinoma between 2000 and 2020 in a tertiary care medical center were retrospectively reviewed. Data collected included demographics, clinical and pathological features, treatment modalities, tumor recurrence data including the diagnostic modality (patient's symptoms, physical examination, or imaging), and outcome. Results: The cohort included 123 patients with advanced-stage laryngeal cancer. Thirty-five (28.7%) patients experienced disease recurrence with fourteen recurrences (40%) diagnosed by imaging. Patients diagnosed by imaging had a shorter time to recurrence diagnosis (23.8 vs. 45.9 months, p-value = 0.016), with similar 5-year overall and disease-specific survival (20.6% vs. 26.6%, log-rank p-value = 0.53 and 62.1% vs. 59.7%, log-rank p-value = 0.87, respectively). Conclusions: Performance of routine post-treatment imaging follow-up in patients with advanced laryngeal cancer was associated with a shorter time to diagnosis of recurrence and similar survival rates. Imaging follow-up should be considered in cases where clinical follow-up is limited and according to the judgment of the treating physician. [ABSTRACT FROM AUTHOR]

Objective: Elective neck dissection (END) improves outcomes among clinically node‐negative patients with oral cavity squamous cell carcinoma (OCSCC). However, END is of questionable value, considering the potentially higher comorbidities and operative risks in elderly patients. Methods: A retrospective review of all patients older than 65 years of age who were treated for OCSCC at a tertiary care centre between 2005 and 2020 was conducted. Results: Fifty‐three patients underwent primary tumour resection alone, and 71 had simultaneous END. Most primary tumours were located on the mobile tongue. The patients who did not undergo END had a higher mean age (81.2 vs. 75.1 years, P < 0.00001), significantly shorter surgeries, and shorter hospitalizations. Occult cervical metastases were found in 24% of the patients who underwent END. The two groups showed no significant differences in overall survival or recurrence rates. Similar results were shown in a subpopulation analysis of patients older than 75 years. Conclusion: Foregoing END in elderly patients with no clinical evidence of neck metastases did not result in lower survival rates or higher recurrence rates. [ABSTRACT FROM AUTHOR]