Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Clinical outcomes in perineural spread of cutaneous squamous cell carcinoma via the ophthalmic nerve.

BACKGROUND: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. OBJECTIVE: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. MATERIALS AND METHODS: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment. RESULTS: Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival. DISCUSSION: Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. CONCLUSION: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

TXNIP-mediated crosstalk between oxidative stress and glucose metabolism.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.