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.

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.

Current ionising radiation doses in the Chernobyl Exclusion Zone do not directly impact on soil biological activity.

Although soil organisms are essential for ecosystem function, the impacts of radiation on soil biological activity at highly contaminated sites has been relatively poorly studied. In April-May 2016, we conducted the first largescale deployment of bait lamina to estimate soil organism (largely soil invertebrate) feeding activity in situ at study plots in the Chernobyl Exclusion Zone (CEZ). Across our 53 study plots, estimated weighted absorbed dose rates to soil organisms ranged from 0.7 µGy h-1 to 1753 µGy h-1. There was no significant relationship between soil organism feeding activity and estimated weighted absorbed dose rate. Soil biological activity did show significant relationships with soil moisture content, bulk density (used as a proxy for soil organic matter) and pH. At plots in the Red Forest (an area of coniferous plantation where trees died because of high radiation exposure in 1986) soil biological activity was low compared to plots elsewhere in the CEZ. It is possible that the lower biological activity observed in the Red Forest is a residual consequence of what was in effect an acute high exposure to radiation in 1986.

Impacts of radiation exposure on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone.

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes have received little attention to date. We present the first analysis of small mammal gut microbiomes from the Chernobyl Exclusion Zone in relation to total absorbed dose rate, including both caecum and faeces samples. We provide novel evidence that host species determines fungal community composition, and that associations between microbiome (both bacterial and fungal) communities and radiation exposure vary between host species. Using ambient versus total weighted absorbed dose rates in analyses produced different results, with the latter more robust for interpreting microbiome changes at the individual level. We found considerable variation between results for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. Associations between radiation exposure and microbiome composition of gut samples were not robust against geographical variation, although we identified families of bacteria (Lachnospiraceae and Muribaculaceae) and fungi (Steccherinaceae and Strophariaceae) in the guts of bank voles that may serve as biomarkers of radiation exposure. Further studies considering a range of small mammal species are needed to establish the robustness of these potential biomarkers.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated "risk of bias" tool to assess study quality. Four separate Phase I-II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5-34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I-III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

CXCR4 and PD-1 Expression in Head and Neck Cancer with Perineural Spread.

Background Perineural spread (PNS) is a marker of aggressiveness and has been shown to occur in cranial nerves due to advanced mucosal and cutaneous head and neck cancer. Receptors CXC chemokine receptor 4 (CXCR4) and programmed cell death-1 (PD-1) have been shown to be overexpressed in a variety of cancers with PNS, with the inhibition of these pathways offering a potential future treatment. Methods Retrospective immunohistochemical staining for the CXCR4 and PD-1 receptors was performed on 28 head and neck specimens that demonstrated PNS from January 2017 to August 2017, at Royal Brisbane and Women's Hospital, Brisbane, Australia. Results CXCR4 staining was positive in 52 and 60% of the squamous cell carcinoma (SCC) and adenoid cystic carcinoma PNS specimens, respectively. Cutaneous SCC tumors with no PNS stained positively in 33%. No significant staining for PD-1 in peritumoral lymphocytes or tumor specimens was seen. Conclusion CXCR4 is overexpressed in advanced skin cancer and head and neck tumors that demonstrated PNS to large cranial nerves. Overall, these results provide strong support for using CXCR4 as a biomarker and further investigation of immunotherapeutic agents that could inhibit tumor progression via targeting CXCR4 expression.

Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1nu and NOD/SCID mice and treated with intratumoral injection of 30 µg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

Nurse confidence in gynaecological oncology practice and the evaluation of a professional development module.

BACKGROUND: A tertiary-based education program on gynaecological oncology was attended by 62 registered nurses (RN). AIMS: The program aimed to update nurses' knowledge, improve skills and ability to manage common situations and to assess program efficacy. DESIGN: Evaluation framework with specifically designed pre-post questionnaire about program content and nurse confidence. METHOD: RN interested in gynaecological oncology were invited to attend. Nurses rated their confidence about gynaecological oncology skills one week prior to the program, immediately post-course, 3 months post and 12 months post. Speaker presentations were evaluated immediately post-course. RESULTS: Participants indicated improved confidence immediately after participating in the course (z = -6.515, p < .001); whilst confidence subsequently declined and stabilised up to 12 months post-course, it still remained significantly higher than before the course: 3 months post- (z = -5.284, p < .001) and 12 months post- (z = -4.155, p < .001). CONCLUSIONS: Results support the value of continuing professional education for improving nurse confidence in the gynaecological oncology setting.

Assessing radiation impact at a protected coastal sand dune site: an intercomparison of models for estimating the radiological exposure of non-human biota.

This paper presents the application of three publicly available biota dose assessment models (the ERICA Tool, R&D128/SP1a and RESRAD-BIOTA) to an assessment of the Drigg coastal sand dunes. Using measured (90)Sr, (99)Tc, (137)Cs, (238)Pu, (239+240)Pu and (241)Am activity concentrations in sand dune soil, activity concentration and dose rate predictions are made for a range of organisms including amphibians, birds, invertebrates, mammals, reptiles, plants and fungi. Predicted biota activity concentrations are compared to measured data where available. The main source of variability in the model predictions is the transfer parameters used and it is concluded that developing the available transfer databases should be a focus of future research effort. The value of taking an informed user approach to investigate the way in which models may be expected to be applied in practice is highlighted and a strategy for the future development of intercomparison exercises is presented.