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Purpose/objectives To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilot® System) to account for intra-fractional organ motion. Material/methods Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED1.5 = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date. Results All patients completed the treatment in the expected time (10.2 +/− 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery. Conclusions Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up.

Northern Italy has been one of the European regions reporting the highest number of COVID‐19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID‐19‐positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID‐19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer‐related outcome. In this article, we attempt to estimate the individual risk–benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID‐19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. Implications for Practice Managing patients with breast cancer during the COVID‐19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID‐19‐related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients’ and health workers’ psychological distress., This article discusses strategies employed by an institution in Northern Italy to ensure the continuum of the best possible cancer care during the COVID‐19 pandemic for breast cancer patients while mitigating the risk of infection, despite limited health care resources.

AIMS To assess if left atrial phasic function characteristics modulate functional capacity/survival by impacting on the pulsatile component of right ventricular (RV) afterload, as represented by pulmonary arterial compliance (PAC). MATERIALS AND METHODS Sixty heart failure patients (67 ± 11 years, ejection fraction 39 ± 11%, range 20--62%) underwent 6 min walk test (6MWT) and 3D transthoracic echocardiography. Left atrial conduit was computed off-line, gathering simultaneous real-time 3D multibeats (six cycles) left atrial and left ventricular (LV) volume curves, with conduit (time) = [LV (time) - LV minimum volume] - [left atrial maximum volume - left atrial (time)], expressed as % LV stroke volume. Atrial stiffness (Kla) was computed using noninvasively assessed wedge pressure divided by left atrial reservoir (maximum - minimum) volume. PAC was obtained as ratio between RV stroke volume, obtained as pulsed Doppler RV outflow tract envelope∗cross-sectional area, and pulmonary pulse pressure, obtained by transforming tricuspid regurgitant velocity in millimetres of mercury and considering diastolic pulmonary as a fixed fraction of systolic pressure. RESULTS Conduit averaged 34 ± 12%, PAC 3.1 ± 1.1 ml/mmHg, 6MWT 404 ± 154 m. Conduit was independent of LV volumes and ejection fraction, showing a direct dependence on noninvasive Kla (r = 0.56; P

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients.

Purpose or Objective To assess the intrafraction accuracy of a frameless stereotactic linac-based radiosurgery (SRS) for brain metastases (BM) using a homemade mouth-bite thermoplastic mask in combination with cone-beam computed tomography (CBCT) and six-degrees of freedom (6-DOF) couchtop. Materials and Methods Covid-19 restrictions resulted in significant delays in the supply of the dedicated devices for BM SRS. A frameless approach using a homemade mouth-bite thermoplastic mask was implemented to offer BM SRS in a period of limited mobility (figure 1). All patients were immobilized and treated at the same institution with 6 MV FFF VMAT radiosurgery, with a 2 mm isotropic expansion from the GTV to the PTV. Before treatment delivery, patients underwent a low-dose CBCT to check position accuracy. Through image co-registration, translational (x, y, z) and rotational errors (roll, pitch, and yaw) were determined. The 6-DOF couchtop was used to automatically relocate the patient with sub-millimetric precision. Immediately after irradiation, patients underwent a second CBCT to verify any translational or rotational errors occurring during therapy (intrafraction motion). $Φg Results From February 2020 to January 2021 sixteen patients (29 lesions) received BM SRS (14-21 Gy). The whole procedure, from the first CBCT scan to the end of irradiation and subsequent CBCT, required a median time of 9 minutes [6-13]. Mean translational error was 0.0 ± 0.3 mm [-0.7;0.9] in lateral direction, and -0.1 ± 0.5 mm [-1.4;1.0] in longitudinal direction. A 2.2 mm maximum shift was recorded on the vertical axis, nevertheless the mean translation error was 0.1 ± 0.6 mm. Roll, pitch and yaw registered a mean value of -0.1 ± 0.3° [-0.8;0.2], 0.0 ± 0.2° [-0.8;0.2], and -0.1 ± 0.3° [-0.8;0.4], respectively. The results are summarized in figure 2. Conclusion This study demonstrated that homemade mouth-bite thermoplastic masks combined with CBCT, 6-DOF couchtop, and fast FFF treatment delivery allow minimal intra-fraction uncertainties in BM SRS, confirming the accuracy of PTV margin definition. The results are comparable to the declared specifics of SRS dedicated commercial frameless mask, while improving patient's comfort compared to the invasive fixed frame. However, the moulding procedure requires improved RTT skills and expertise. Our findings show that SRS can be safely delivered in radiotherapy units without dedicated expensive installations, such as CyberKnife and Gamma Knife, thus reducing patient mobility according to Covid-19 restrictions.

Background: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. Methods: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Results: Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26–4.45, p < 0.01) and 2.58 (95% CI 1.40–4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00–3.35, p = 0.04)]. Smoking status did not predict for CSS. Conclusion: Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.

Objective: Obesity is characterized by a state of chronic, low-intensity systemic inflammation frequently associated with insulin resistance and dyslipidemia. Materials and methods: Given that chronic inflammation has been implicated in the pathogenesis of mood disorders, we investigated if chronic obesity that was initiated early in life – lasting through adulthood – could be more harmful to memory impairment and mood fluctuations such as depression. Results: Here we show that pre-pubertal male rats (30 days old) treated with a high-fat diet (40%) for 8-months gained ~50% more weight when compared to controls, exhibited depression and anxiety-like behaviors but no memory impairment. The prefrontal cortex of the obese rats exhibited an increase in the expression of genes related to inflammatory response, such as NFKb, MMP9, CCl2, PPARb, and PPARg. There were no alterations in genes known to be related to depression. Conclusion: Long-lasting obesity with onset in prepuberal age led to depression and neuroinflammation but not to memory impairment.

We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Contains fulltext : 220257.pdf (Publisher’s version ) (Closed access) The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Background: Head and neck squamous cell carcinoma, and in particular hypopharyngeal squamous cell carcinoma, has long been associated with disfiguring treatment options, significant morbidity and limited long-term survival outcomes. Total pharyngolaryngectomy (TPL) with free flap reconstruction followed by post-operative radiation therapy or chemoradiotherapy is a widely accepted treatment of choice for advanced disease of the hypopharynx. Methods: Our unit undertook a 11-year review of all primary TPL patients aiming to provide an update on survival outcomes, morbidity, post-operative complications and evolving management strategies. We report one of the largest single-centre series to date with 89 patients undergoing primary TPL between 2003 and 2013, and compare these outcomes to 180 patients undergoing TPL at the same facility in the previous 23 years. Results: Between study periods, we saw a shift in patient population towards higher stage disease (T-stage 3 or 4 97% 2003–2013; 68% 1979–2002) and increased nodal involvement (node positive 88% 2003–2013; 70% 1979–2002) without a subsequent reduction in 5-year disease-specific survival (52% 2003–2013; 52% 1979–2002) or 5-year overall survival (32% 2003–2013; 33% 1979–2002).

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.

This article provides an overview of the natural history and management of adenoid cystic carcinoma infiltrating the skull base (SB ACC). A comprehensive review of the available literature and discussion regarding the current management of SB ACC. This review describes the unique pathology, appropriate diagnostic work-up and contemporary management options in SB ACC. There is a specific focus on the role of surgical resection with post-operative radiotherapy, given the literature suggesting a superior locoregional control rate. The importance of surgical decision making and varying surgical approaches are detailed. In addition, the emerging role of biological agents is discussed. The gold standard for SB ACC is surgical resection and post-operative radiation, given the superior locoregional control. In patients not amendable to surgery, palliative radiation should be considered. The role of biological agents is still evolving. The complexity of SB ACC management mandates experienced multi-speciality management.

Background: Tigilanol tiglate, a short-chain diterpene ester, is being developed as intratumoral treatment of a broad range of cancers. We conducted the first-in-human study of intratumoral tigilanol tiglate in patients with solid tumors. Methods: Tigilanol tiglate was administered in a multicentre, non randomized, single-arm study, with escalating doses beginning with 0·06 mg/m2 in tumors estimated to be at least twice the volume of injection (dose-escalation cohorts). Patients with smaller tumors were assigned to the local effects cohort and received the appropriate dose for tumor size. Findings: Twenty-two patients were enrolled. The maximum dose was 3·6 mg/m2 and the maximum tolerated dose was not reached. There was one report of dose-limiting toxicity (upper airway obstruction), two serious adverse events (upper airway obstruction and septicemia), 160 treatment-emergent adverse events, and no deaths. Injection site reactions in all tumors and tumor types occurred even at the lowest dose. Six of the 22 patients experienced a treatment response, with four of the six patients achieving complete response. Interpretation: Intratumoral tigilanol tiglate was generally well tolerated, the maximum tolerated dose was not reached, and clinical activity was observed in 9 tumor types including complete response in four patients. These results support the continued development of tigilanol tiglate for intratumoral administration. Funding: QBiotics Group Limited Brisbane, Queensland, Australia was the sponsor of the study. Keywords: Diterpene ester, EBC-46, Intratumoral, Protein kinase C, Tigilanol tiglate

To demonstrate safety of a developed intranasal dexamethasone-infused in situ gelling formulation, quantification of a validated clinical biomarker indicative of cytotoxic potential using a human sinonasal explant model was first confirmed. Systematic cytotoxicity studies using the lactate dehydrogenase (LDH) detection assay revealed no elevation from baseline, in LDH levels, with tissue integrity of explanted human nasal mucosa also maintained; this was further corroborated using tissue histopathological examination. Next, with safety confirmed ex vivo, freshly excised human nasal tissue was utilised to quantify dexamethasone release from the lead sol–gel systems; this being achieved through development and validation of a HPLC-UV analytical method, which reliably quantified controlled therapeutic release and deposition into mucosal tissue. Collectively, these findings indicate promise in the safety of each excipient within the concentrations employed in the functional sol–gel system, complemented by successful and reliable drug release and deposition into human nasal mucosal tissue. These findings pave the way for application of the dexamethasone-based sol–gel system to the extended delivery of corticosteroids to nasal mucosa in the management of localised inflammatory conditions of an acute and chronic nature, such as chronic rhinosinusitis, which can be expected to benefit from controlled and extended drug delivery characteristics imparted by appropriately engineered in situ gelling systems. Keywords: Intranasal soluble gels, Sinusitis, Explant human nasal mucosa, Tissue toxicity, LDH assay, Drug deposition in human nasal mucosa

An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarita ed Ereditarieta dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).

Background: Recent evidence supports a role of probiotics in preventing necrotizing enterocolitis (NEC) in preterm infants. Methods: A systematic review and network meta-analysis of randomized controlled trials (RCTs) on the role of probiotics in preventing NEC in preterm infants, focusing on the differential effect of type of feeding, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used; a subgroup analysis on exclusively human milk (HM)-fed infants vs. infants receiving formula (alone or with HM) was performed. Results: Fifty-one trials were included (10,664 infants, 29 probiotic interventions); 31 studies (19 different probiotic regimens) were suitable for subgroup analysis according to feeding. In the overall analysis, Lactobacillus acidophilus LB revealed the most promising effect for reducing NEC risk (odds ratio (OR), 0.03; 95% credible intervals (CrIs), 0.00–0.21). The subgroup analysis showed that Bifidobacterium lactis Bb-12/B94 was associated with a reduced risk of NEC stage ≥2 in both feeding type populations, with a discrepancy in the relative effect size in favour of exclusively HM-fed infants (OR 0.04; 95% CrIs B. lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type. Of note, most probiotic strains are evaluated in few trials and relatively small populations, and outcome data according to feeding type are not available for all RCTs. Further trials are needed to confirm the present findings.

Insights into imaging 12(1), 119 (2021). doi:10.1186/s13244-021-01062-x, Published by Springer, Heidelberg

In case of severe acute respiratory distress syndrome (ARDS), as in coronavirus disease 2019 (COVID-19) affected patients, the invasive ventilation in prone position can improve the prognosis, albeit with an increased risk of facial pressure ulcers. In this report, we will relate a case of facial pressure ulcers in a SARS-CoV-2 positive 50 year-old woman with the aim to describe the high-complexity management of COVID 19 in which healthcare professionals across the world are still involved.

Malignancies in and around the temporal bone are aggressive and difficult to manage. In Queensland (Australia), where skin cancer rates are exceedingly high, tumours extending to the temporal bone from surrounding structures occur more commonly than primary cancers. Yet, a paucity of evidence exists as to their management and outcomes. This study aimed to review an Australian centre's experience of managing temporal and peritemporal bone malignancies, reporting on patient and tumour characteristics, treatment, and survival outcomes.Retrospective analysis of patients with primary temporal bone cancer and cancers extending to the temporal bone managed by the Queensland Skull Base Unit (Princess Alexandra Hospital) between 2000 and 2019.A total of 222 patients were identified, of which 203 (91.4%) had cutaneous primaries, with 167 (75.2%) being squamous cell carcinoma (SCC). 73.9% presented with locoregionally recurrent or residual disease. Secondary tumours (92.8%) were 12 times more frequent than primary malignancies (7.2%), with the preauricular subsite the most common (45.5%). In the 201 patients (90.5%) who underwent curative intent surgery, 5-year overall survival, disease-free survival (DFS), and disease-specific survival was 46.6%, 52.2%, and 65.9%, respectively. The preauricular subsite (p = 0.004), melanoma (vs. SCC, p = 0.027), involved margins (p 0.001), and pathologically involved nodes (p 0.001) were associated with significantly worse DFS.This is one of the largest studies of temporal bone malignancy in the literature, comprised primarily of secondary cutaneous malignancies. Although clear differences in epidemiological characteristics exist around the world, survival remains poor. Treatment should focus on achieving a clear margin of resection to optimize outcomes.

Patients with borderline personality disorder (BPD) often display increased stress vulnerability, which may be linked to altered hypothalamus–pituitary–adrenal (HPA) axis functioning. Corresponding deviations of the cortisol awakening response (CAR) are presumed to mirror maladaptive neuroendocrine processes, which may explain why CARs are increased compared to healthy controls (HC). Prior research speculated that these alterations may be caused by early life stress and/or chronic stress related to the ongoing burden of the disorder. Yet, it remains to be investigated how BPD influences CAR in the course of development. Therefore, the current study examined CAR in female adolescents and adults with BPD compared to HC with a particular focus on associations with age. These potential associations were especially focused, as it was hypothesized that the CAR would be even more elevated (i.e., higher) in older individuals with BPD. CAR was assessed in 54 female individuals with BPD (aged 15–40 years) and 54 sex-, age-, and intelligence-matched HC (aged 15–48 years). Group differences were investigated and analyses of covariance using age as continuous predictor were performed to analyze potential developmental associations with CAR alongside BPD-specific effects. Pearson’s correlations were calculated to examine associations between CAR and age. Analyses were repeated with potential confounders as control factors. Results not only demonstrated increased CARs in female individuals with BPD compared to HC but demonstrated elevated CARs with increasing age in BPD individuals exclusively. Effects remained stable after controlling for potential confounders. Thereby, findings suggest that endocrine alterations in BPD may reinforce with increasing age and BPD chronicity.

Simple Summary PET/MRI is a relatively new, hybrid imaging tool that allows practitioners to obtain both a local and systemic staging in breast cancer patients in a single exam. To date, the available evidence is not sufficient to determine the role of PET/MRI in breast cancer management. The aims of this paper are to provide an overview of the current literature on PET/MRI in breast cancer, and to illustrate two ongoing trials aimed at defining the eventual role of PET/MRI in axillary staging in two different settings: patients with early breast cancer and patients with positive axillary nodes that are candidates for primary systemic therapy. In both cases, findings from PET/MRI will be compared with the final pathology and could be helpful to better tailor axillary surgery in the future. Abstract Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

The natural history of adenoid cystic carcinoma (ACC) is relentless, defined by treatment failure heralded by reasonable locoregional recurrence and poor long-term distant metastatic disease. In this review, we present an update of clinical features, molecular classification, current targeted therapies, immune landscapes and novel treatment targets with their respective clinical trials. The presented results are defined by a lack of overall response rate and limited progression free survival, with restriction to stable. In addition, ACC is resistant to immune checkpoint inhibition due to low tumour immunogenicity and lack of PD-L1 expression. Here we present a new prospective research paradigm for ACC, including the potential to target prostate specific membrane antigen (PSMA) and the potential for manipulation of target receptors in the clinic. The presentation of this review aims to promote future research to improve response rates and outcomes for therapeutics undergoing clinical trial in ACC.

Highlights • RFA is an effective minimally invasive treatment for selected patients with primary and secondary lung tumors. • We described the expected imaging features after RFA of lung tumors, and their frequency over time after the procedure. • Radiologists should be familiar with these features in order to avoid misinterpretation and inadequate treatments. • These normal post-procedure imaging features must be considered in future post-ablation follow-up protocols., Purpose To describe expected imaging features on chest computed tomography (CT) after percutaneous radiofrequency ablation (RFA) of lung tumors, and their frequency over time after the procedure. Methods In this double-center retrospective study, we reviewed CT scans from patients who underwent RFA for primary or secondary lung tumors. Patients with partial ablation or tumor recurrence during the imaging follow-up were not included. The imaging features were assessed in pre-defined time points: immediate post-procedure, ≤4 weeks, 5−24 weeks, 25−52 weeks and ≥52 weeks. Late follow-up (3 and 5 years after procedure) was assessed clinically in 48 patients. Results The study population consisted of 69 patients and 144 pulmonary tumors. Six out of 69 (9%) patients had primary lung nodules (stage I) and 63/69 (91 %) had metastatic pulmonary nodules. In a patient-level analysis, immediately after lung RFA, the most common CT features were ground glass opacities (66/69, 96 %), consolidation (56/69, 81 %), and hyperdensity within the nodule (47/69, 68 %). Less than 4 weeks, ground glass opacities (including reversed halo sign) was demonstrated in 20/22 (91 %) patients, while consolidation and pleural thickening were detected in 17/22 patients (77 %). Cavitation, pneumatocele, pneumothorax and pleural effusions were less common features. From 5 weeks onwards, the most common imaging features were parenchymal bands. Conclusions Our study demonstrated the expected CT features after lung RFA, a safe and effective minimally invasive treatment for selected patients with primary and secondary lung tumors. Diagnostic and interventional radiologists should be familiar with the expected imaging features immediately after RFA and their change over time in order to avoid misinterpretation and inadequate treatments.

Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.

Background and purpose Human papillomavirus-associated oropharyngeal cancer (HPV+ OPC) with regional lymph node metastases has a good prognosis following (chemo)radiation therapy (C/RT) but lymph nodes may remain detectable for several months. Delayed [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) can identify patients who may avoid post-treatment neck dissection (PTND). We investigated the rate of PTND in HPV+ OPC treated with C/RT and delayed PET-directed management of the neck. Materials and methods This is a retrospective cohort study from a prospectively updated institutional database. Eligible patients were treated between January 2005 and July 2017 with a minimum of 18 months follow up, had node-positive, non-distant metastatic HPV+ OPC and were treated with RT (70 Gy/35#/5 per week) with concurrent Cisplatin or Cetuximab, or accelerated RT alone (68 Gy/34#/6 per week). The primary endpoint was rate of PTND. Secondary endpoints were locoregional failure free survival (LRFFS), regional failure free survival (RFFS), distant metastatic failure free survival (DMFFS), overall survival (OS) and oropharyngeal cancer-specific survival (CSS). Results 418 patients were eligible. Nineteen patients (4.5%) received a PTND. None of the tested variables were associated with an increased risk of PTND. Five-year probabilities for LRFFS, RFFS, DMFS, OS and CSS were, 91.2% (95% CI 88.3–94.2), 93.4% (95% CI 90.8–96.0), 91.2% (95% CI 88.3–94.2), 86.4% (95% CI 83.0–90.1) and 90.2% (95% CI 87.1–93.4), respectively. Conclusion In a large cohort with good median follow up and protocolized C/RT, delayed PET-directed management of the neck affords a lower rate of PTND than reported in historical series without compromising disease control and survival.

Author(s): Panizza, Chloe E; Wong, Michael C; Kelly, Nisa; Liu, Yong En; Shvetsov, Yurii B; Lowe, Dylan A; Weiss, Ethan J; Heymsfield, Steven B; Kennedy, Samantha; Boushey, Carol J; Maskarinec, Gertraud; Shepherd, John A | Abstract: BackgroundVisceral adiposity, more so than overall adiposity, is associated with chronic disease and mortality. There has been, to our knowledge, little research exploring the association between diet quality and visceral adipose tissue (VAT) among a mulitethnic population aged 18-80 y.ObjectiveThe primary objective of this cross-sectional analysis was to examine the association between diet quality [Healthy Eating Index-2010 (HEI-2010) scores] and VAT among a multiethnic population of young, middle, and older aged adults in the United States. Secondary objectives were to repeat these analyses with overall adiposity and blood-based biomarkers for type 2 diabetes and cardiovascular disease risk as outcome measures.MethodsA total of 540 adults (dropped out: nn=n4; age: 18-40 y, nn=n220; 40-60 y, nn=n183; 60-80 y, nn=n133) were recruited across 3 sites (Honolulu County, San Francisco, and Baton Rouge) for the Shape Up! Adults study. Whole-body DXA, anthropometry, fasting blood draw, and questionnaires (food frequency, physical activity, and demographic characteristics) were completed. Linear regression was used to assess the associations between HEI-2010 tertiles and VAT and secondary outcome measures among all participants and age-specific strata, while adjusting for known confounders.ResultsVAT, BMI (kg/m2), body fat percentage, total body fat, trunk fat, insulin, and insulin resistance were inversely related to diet quality (all P values ln0.004). When stratified by age, diet quality was inversely associated with VAT among participants aged 60-80 y (P ln0.006) and VAT/subcutaneous adipose tissue (SAT) among participants aged 40-60 y (P ln0.008).ConclusionsHigher-quality diet was associated with lower VAT, overall adiposity, and insulin resistance among this multiethnic population of young, middle, and older aged adults with ages ranging from 18 to 80 y. More specifically, adherence to a high-quality diet may minimize VAT accumulation in adults aged 60-80 y and preferentially promote storage of SAT compared with VAT in adults aged 40-60 y.This study was registered at clinicaltrials.gov as NCT03637855.

Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease. Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto-staining platform for EGFR, PD-1, PD-L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD-L1 positive cases and log-rank testing was performed to examine the relationship between PD-L1 expression status and disease-free survival (DFS) and overall survival (OS). CPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P = .021), advanced pathological N status (P = .006), high histological tumor grade (P = .045), and positive histological margin (P = .023). Patients with PD-L1 positivity in tumor cells did not have an inferior 3-year OS (P = .93). The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response.

Prostate adenocarcinoma is the most common prostate cancer; however, there are several other malignant neoplasms that radiologists should be familiar with. The histological classification of malignant prostate neoplasms includes epithelial tumors, mesenchymal tumors, neuroendocrine tumors, hematolymphoid tumors, and stromal tumors. Knowledge of the main clinical and prostate magnetic resonance imaging features of uncommon tumors beyond adenocarcinoma is important for radiologists to enlarge their diagnostic ability and guide referring physician regarding the appropriate patient workup.The aim of this review article is to (1) review the main anatomical and histological concepts of the prostate gland and (2) provide an overview of uncommon prostate malignant neoplasms, emphasizing the key clinical, pathological, and imaging findings that may help radiologists in their daily interpretation of prostate magnetic resonance imaging.

Background/Objectives: Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair‐skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non‐representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients. Methods: We retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population‐based cohort of 43 794 Queensland residents recruited 2010–2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high‐risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012–2014.) We estimated the prevalence of perineural invasion (and 95% confidence interval) in BCC and SCC, respectively, and identified clinical factors associated with perineural invasion. Results: In QSkin, we observed 35 instances of perineural invasion in 9850 histopathologically confirmed BCCs (0.36%) and 9 instances of perineural invasion in 3982 confirmed SCC (0.23%) lesions. In the STAR cohort, we identified 4 lesions with perineural invasion in 692 BCCs (0.58%) and 16 reports of perineural invasion in 875 SCC lesions (1.9%). Conclusions: These data suggest that the overall prevalence of perineural invasion in keratinocyte cancer is low, although perineural invasion prevalence may be slightly higher among organ transplant recipients when compared to the general population.

To improve the specificity of breast cancer diagnosis SOLUS combines ultrasound, shear-wave elastography and time-domain diffuse optical tomography in a multimodal imaging system. An innovative compact device for time-domain multi-wavelength diffuse optics was also developed.

The Italian College of Breast Radiologists by the Italian Society of Medical Radiology (SIRM) provides recommendations for breast care provision and procedural prioritization during COVID-19 pandemic, being aware that medical decisions must be currently taken balancing patient’s individual and community safety: (1) patients having a scheduled or to-be-scheduled appointment for in-depth diagnostic breast imaging or needle biopsy should confirm the appointment or obtain a new one; (2) patients who have suspicious symptoms of breast cancer (in particular: new onset palpable nodule; skin or nipple retraction; orange peel skin; unilateral secretion from the nipple) should request non-deferrable tests at radiology services; (3) asymptomatic women performing annual mammographic follow-up after breast cancer treatment should preferably schedule the appointment within 1 year and 3 months from the previous check, compatibly with the local organizational conditions; (4) asymptomatic women who have not responded to the invitation for screening mammography after the onset of the pandemic or have been informed of the suspension of the screening activity should schedule the check preferably within 3 months from the date of the not performed check, compatibly with local organizational conditions. The Italian College of Breast Radiologists by SIRM recommends precautions to protect both patients and healthcare workers (radiologists, radiographers, nurses, and reception staff) from infection or disease spread on the occasion of breast imaging procedures, particularly mammography, breast ultrasound, breast magnetic resonance imaging, and breast intervention procedures.

Recent studies have evidenced the potential of combining anti-EGFR therapies with anti-PD-1/PD-L1 checkpoint therapies. Both anti-EGFR and anti-PD-1/PD-L1 have been separately tested in the treatment of cutaneous SCC (cSCC). Here, we review recent data on EGFR in the context of cancer progression, as a prognostic and as a therapeutic target in cSCC. Anti-EGFR/checkpoint immunotherapy and other combination therapy approaches are discussed. With the advent of immunotherapy, EGFR is still a valid cSCC target.

Lipomas of the gastrointestinal tract are uncommon benign tumors of mature adipocytes and may occur in any portion along the gut. Depending on location they may have a variety of clinical presentations and even simulate malignant neoplasms. We report a case of a 58-year-old woman who presented with acute pelvic pain. An emergency sonogram detected a hyperechogenic mass in the left adnexal region, with no vascularization on Doppler. A computed tomography confirmed the hypothesis of a fat containing tumor with signals of torsion. The patient underwent laparoscopy which depicted a mass over the antimesenteric side of the sigmoid with signs of ischemia and twisted vascular pedicle. The lesion was resected, and the microscopy confirmed the diagnosis of lipoma. The multidisciplinary team in the emergency room must be aware of these possible complications in order to optimize patient care. Keywords: Lipoma, Acute abdomen, Ischemia, Computed tomography

Objective:To prospectively evaluate the incidence, risk factors and natural history of postoperative cerebral venous sinus thrombosis (pCVST) in translabyrinthine vestibular schwannoma microsurgical resection and propose a potential management paradigm.Study Design:Prospective, single cohort, multicenter study.Setting:State-wide academic tertiary referral centers.Patients:Fifty-four consecutive patients who underwent translabyrinthine vestibular schwannoma resection.Main Outcome Measures:Incidence of pCVST on postoperative imaging on Day 7, Day 28, and 12 months postoperatively. Patients and tumor characteristics, risk factors, length of stay, intraoperative parameters, complications, and follow-up were analyzed.Results:pCVST was demonstrated in 21 patients (38.9%) on postoperative imaging. All patients with pCVST were treated conservatively and remained asymptomatic in the immediate postoperative period and long-term follow-up. There were no instances of venous infarction, intracranial hemorrhage, or neurological deficits. A majority (61.1%) of pCVST recannalised on long-term follow up with conservative management. There was a statistical association with pCVST and surgery on the side of the non-dominant cerebral venous drainage (n=17, 80.1%, p=0.034). Patients with pCVST were significantly more likely to have a postoperative cerebrospinal fluid (CSF) leak (n=5, 23.8%, p=0.017).Conclusion:The incidence of pCVST following translabyrinthine vestibular schwannoma resection is much higher than previously recognized. pCVST is more likely to occur when surgery is performed on tumors situated on the side of non-dominant cerebral venous drainage. Despite the high prevalence of this iatrogenic phenomenon, all patients were asymptomatic and a majority resolved, thereby suggesting that conservative management is safe. Correlation between pCVST and increased incidence of CSF leak requires further investigation.

The purpose of this study was to examine the relationship between physical impairments, quality of life and disability in patients following neck dissection, with consideration of patient and clinical characteristics. Cross-sectional study of patients

Summary 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.

Ovarian cancer (OC) is the leading cause of gynecological cancer death, and most cases are diagnosed at advanced stages due to a nonspecific and insidious clinical presentation. Radiologists play a critical role in the decision of which patients are candidates for primary debulking surgery and who may benefit from neoadjuvant chemotherapy. This pictorial review summarizes the dissemination patterns of OC, main imaging findings of metastatic disease, and which findings may alter the treatment plan or predict suboptimal tumor resection.

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient’s autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking.

Breast screening with mammography is the most effective method of detecting early-stage breast cancer and reducing related mortality. Among the intrinsic limits of mammography, in terms of clinical performance, the overlapping of normal and pathological tissues is one of the most influential. Some new techniques as Digital Breast Tomosynthesis (DBT) is expected to overcome this limitation by providing a quasi-three-dimensional (3D) image that could lead to improve the accuracy of mammography. Another way to increase accuracy and sensitivity is represented by a double exposure of the patient before and after intravenous injection of contrast media, this technique is called Contrast-enhanced digital (or spectral) mammography (CEDM, CESM). Furthermore, highly specialized software has been developed which is able to detect suspicious mammographic findings. This technology is very interesting especially in the screening field, in fact there are multiple ongoing studies evaluating the use of Artificial Intelligence (AI) as a second reader. To date, screening mammography is the only imaging modality that has proven to significantly lower breast cancer mortality. Tomosynthesis demonstrated excellent sensitivity and specificity but the technique did not meet the expectations given the risk of over diagnosis as well as the lack of reduction in the number of interval breast cancer. CESM could in some cases serve as an alternative imaging tool to MRI. AI, seems to be competing with the breast radiologist and its use as a second reader in breast screening programs is already being proposed.

Patients with head and neck cancer can report reduced health-related quality of life several years after treatment. The aim of this study was to identify risk factors for reduced quality of life in patients up to 5 years following neck dissection. This cross-sectional study was conducted at two hospitals in Brisbane, Australia. Patients completed two measures of quality of life: the Neck Dissection Impairment Index (NDII), a region- and disease-specific tool, and the Assessment of Quality of Life-4 Domains, a general tool. Generalised linear modelling was used to determine which demographic and clinical variables were associated with quality of life. The cohort included n = 129 patients (71% male, median age 61, median 3 years since surgery). Positive nodal disease was associated with better quality of life on the NDII [e.g. N2 vs N0 coeff (95% CI) = 22.84 (7.33, 38.37)]. Worse quality of life was associated with adjuvant treatment [e.g. Independent Living domain model: surgery with chemoradiation vs surgery only coeff (95% CI) = -0.11 (-0.22, -0.01)]. Positive nodal disease was associated with better quality of life, which may be a reflection of response shift. Multimodality treatment leads to worse quality of life compared with surgery only.

Introduction\ud Shoulder pain and dysfunction may occur following neck dissection among people being treated for head and neck cancer. This systematic review aims to examine the prevalence and incidence of shoulder and neck dysfunction after neck dissection and identify risk factors for these post-operative complications.\ud \ud Methods\ud Electronic databases (Pubmed, CINAHL, EMBASE, Cochrane) were searched for articles including adults undergoing neck dissection for head and neck cancer. Studies that reported prevalence, incidence or risk factors for an outcome of the shoulder or neck were eligible and assessed using the Critical Review Form – Quantitative Studies.\ud \ud Results\ud Seventy-five articles were included in the final review. Prevalence rates for shoulder pain were slightly higher after RND (range, 10–100%) compared with MRND (range, 0–100%) and SND (range, 9–25%). The incidence of reduced shoulder active range of motion depended on surgery type (range, 5–20%). The prevalence of reduced neck active range of motion after neck dissection was 1–13%. Type of neck dissection was a risk factor for shoulder pain, reduced function and health-related quality of life.\ud \ud Conclusions\ud The prevalence and incidence of shoulder and neck dysfunction after neck dissection varies by type of surgery performed and measure of dysfunction used. Pre-operative education for patients undergoing neck dissection should acknowledge the potential for post-operative shoulder and neck problems to occur and inform patients that accessory nerve preservation lowers, but does not eliminate, the risk of developing musculoskeletal complications.

Objectives To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV + OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). Material and methods The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. Results A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6–100%), Stage III 93.8% (95% CI; 85.9–100%), Stage IVa 86.4% (95% CI; 81.6–91.5%) and Stage IVb 62.3% (95% CI; 46.8–82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p = 0.98, HR = 0.97, 95% CI; 0.11–8.64), IVa (p = 0.67, HR = 1.56, 95% CI; 0.2–11.94) and IVb (p = 0.11, HR = 5.54, 95% CI; 0.69–44.52), respectively. The 5-year OS with ICON-S staging were Stage I 93.6% (95% CI; 89.4–98.0%), Stage II 81.9% (95% CI; 73.7–91.1%) and Stage III 69.1% (95%; 57.9–82.6%). There was a consistent decrease of OS with increasing stage. On multivariate Cox regression analysis, when compared to Stage I, OS was significantly lower for stage II (p = 0.007, HR = 2.84, 95% CI; 1.33–6.05) and stage III (p Conclusion The ICON-S staging provides better OS stratification for HPV + OPC following RT compared with the 7th Ed TNM staging.

Inflammatory breast cancer represents a rare condition that presents poor prognosis with high risk of recurrences and greatly affects patients’ quality of life. The resective surgical treatment frequently requires challenging reconstructive solutions to restore a proper tissue layer for the chest wall. Reconstructive methods are nowadays still matter of debate. A retrospective review of all cases of massive inflammatory breast cancer that underwent mastectomy and reconstruction with fasciocutaneous flaps from October 2009 to September 2014 was performed at our department. Patient demographics, indications, flap specifics, complications, and number of operations were collected. Our review identified five cases. A lateral thoracic flap was planned in two cases, a modified lateral thoraco-dorsal flap in one case, a combination of scapular and pubic flaps in other case, and a thoraco-epigastric and lateral thoracic flap association in the remaining case. The mean patient age was 60 years (range, 35 to 76 years). Flap dimensions ranged from 9cm to 14 cm in width and 20 to 24 cm in length. Partial necrosis of the flap distal part occurred in two cases requiring minor flap revision. Resective surgical treatment of inflammatory breast cancer might require a challenging reconstructive planning. In this scenario, fasciocutaneous flaps are an interesting option due to their versatility, easiness of harvesting, low morbidity, and complications rate. Level of Evidence: Level IV, therapeutic study.

Background It has been suggested that left atrial (LA) characteristics modulate the functional capacity in heart failure (HF) patients through the impact that LA cavity exerts on the pulmonary circulation and the pulsatile component of right ventricular (RV) afterload, as represented by pulmonary arterial compliance (PAC). Purpose Thus, we hypothesized that, in a HF patients' population, a larger relative contribution of LA phasic conduit function (PCF) to the left ventricular (LV) stroke volume would be associated with a heavier right ventricular hemodynamic burden and a reduced functional capacity. Methods 60 sinus rhythm HF subjects (42 males, 67±11 years, ejection fraction [EF] 39±11%, range 20% - 62%) underwent 6 minute walking test (6MWT) and routine transthoracic echocardiography, plus real time 3D acquisitions analyzed with a dedicated echo software package. LV ejection fraction (EF) was obtained from 3D echo acquisitions. LV diastolic dysfunction (DD) was assessed according to current guidelines. Computation of PCF was made by simultaneous gathering real time 3D multibeats (6 cycles) LA and LV volumes, using the formula: PCF(time) = [LV(time) − LV minimum] − [LA maximum − LA(time)] as proposed by Bowman & Kovacs (2004), with PCF expressed as % of LV stroke volume. Atrioventricular compliance (Cn) was also assessed, as proposed by Flachskampf et al. (1992): 1270*(mitral valve area/E wave downslope) and expressed in ml/mmHg. Finally, PAC was obtained as the ratio between RV stroke volume (pulmonary velocity time integral*pulmonary valve annulus area measured from the RV outflow tract diameter) and pulse pressure (obtained from pulmonary and tricuspid regurgitant envelopes) and expressed in ml/mmHg. Results Maximal LA and LV volumes averaged 69±21 ml and 147±47 ml, respectively. The mean value of PCF was 33±12% (range 7% - 58%). Mean 6MWT was 397±162 m. Mean PAC was (3.1±1.1 ml/mmHg). DD grade I, II and III were detected in 38 (63%), 18 (30%) and 4 (7%) of the patients' population, respectively. PCF was independent of LA or LV volumes and EF, but showed a strong direct relation with DD (r=0.62; p Conclusion PCF is an important parameter to be quantified in HF patients that is dependent on global left heart compliance, being affected by DD, but not LV EF. Furthermore, at a given Cn, PCF is increased in HF patients with lowest functional capacity, likely because RV pulsatile afterload is highest in these subjects.

Background Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with a propensity for perineural spread and diffuse soft tissue infiltration. In the head and neck this unique biological behaviour can result in skull base involvement. A lack of consensus regarding management of ACC involving the skull base in conjunction with the technical and reconstructive challenges of oncological resection in this region has led to variation in practice between institutions. Method Retrospective multicentre review of patients with advanced ACC infiltrating the skull base, treated surgically by the Queensland Skull Base Unit between 2005 and 2017, with a minimum follow up time of 24 months. Results 32 patients were treated for ACC with skull base involvement with oncological resection and post-operative radiation in the study period with a median follow up of 82.18 months (33.11–159.53 months). 5 and 10 year locoregional control were both 88.2% (95% CI 67.5–96.1) despite a high rate of microscopically positive margins (81.3%). Metastatic disease rates were high, resulting in low rates of disease free survival (DFS) (53.0% at 5 years (95% CI 33.7–69.0) and 23.0% at 10 years (9.5–39.8)). Overall survival (OS) was high (5 year 91.8% (95% CI 71.1–97.9), 10 year 63.7% (95% 37.5–81.2)), despite the advanced nature of disease. Conclusion High rates of locoregional control can be achieved in skull base ACC with oncological resection of disease and post-operative radiation. Whilst disease recurrence rates are high, a majority of recurrence is metastatic and does not confer poor intermediate term overall survival.

Background/Objectives: Perineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols. Methods: We retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post‐definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion. Results: There was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves

Aortic stenosis is a frequent valvular disease, with transcatheter aortic valve implantation (TAVI) being performed when surgical replacement is at increased risk. However, TAVI-induced effects on myocardial efficiency are unknown. We aimed to investigate changes in LV mechano-energetic pre-/post-TAVI and their prognostic impact. A total of 46 patients (25 males) received transesophageal and simultaneous radial pressure plus transaortic gradient monitoring before/immediately after prosthesis deployment. Efficiency was computed as external work/potential energy, as derived from LV pressure–volume plots; myocardial oxygen consumption (MVO2) was estimated as PWImod, i.e. a noninvasively validated alternative for MVO2 estimation. TAVI was successful in all patients, peak transaortic gradient decreasing − 40 ± 20 mmHg (p 0.021 (17%), particularly in those patients with a pre-TAVI mean high-gradient (HG ≥ 40 mmHg) phenotype (p < 0.05). In particular, HG patients exhibited the lowest efficiency/PWImod ratio pre-/post-TAVI (p = 0.048), relative to the other aortic stenosis patients, suggestive of an unfavourable matching between cardiac function and metabolic demand, which foreshortens some intrinsic damaged muscle condition in these patients. LV mechanical efficiency improves immediately post-TAVI, notwithstanding an inhomogeneous mechano-energetic matching among the aortic stenosis patients, which can impact negatively on their long-term prognosis, particularly in those with the HG phenotype.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.