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The grave offerings and the traces of ritual actions should prove a valuable source for speculation about views on death in antiquity. In the Classical necropolis of Medma the main features of grave’s goods reflect socio-religious believes about death and after death not completely explained yet. In this research suggestions could derive from the analysis of the vegetal charred offers discovered in some burials; they’re figs, olive stones, grapes, almond and, pheraphs, nuts laid inside the tombs, in most cases primary cremations, or in isolated cases above them. Their presence also in religious contexts like sanctuaries suggests ritual and votive actions more than luxury demonstrating, conclusion drawn from the analysis of the terracotta offers too. In Greek tradition the fruits considered are related to the meanings of civilisation, prosperity, wealth and nature renovation and for this holy to nether deities associated to burial rituals.

Background The purpose of this study was to present our evaluation of the outcomes of concurrent chemoradiotherapy (CRT) in patients with locally advanced cutaneous squamous cell carcinoma (SCC). Methods This was a prospective phase II study. The primary endpoint was complete response (CR). Patients with locally/regionally advanced cutaneous SCC deemed unsuitable for surgery received definitive radiotherapy (RT; 70 Gy in 35fractions) and concurrent weekly platinum-based chemotherapy (cisplatin 40 mg/m2 or carboplatin area under the curve 2). Results Twenty-one patients were enrolled in this study. Eighteen patients had a locally advanced primary or nodal disease in the head and neck region with 66% having stage IV nonmetastatic disease. Of 19 evaluable patients, 10 achieved a CR to definitive CRT with 2 further patients rendered disease-free by salvage surgery for an overall CR of 63%. Conclusion This is the only prospective series of CRT for cutaneous SCC. A high CR rate was documented in patients with locoregional advanced disease who were unable to undergo surgery. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The purpose of this study was to present our evaluation of the outcomes of concurrent chemoradiotherapy (CRT) in patients with locally advanced cutaneous squamous cell carcinoma (SCC).This was a prospective phase II study. The primary endpoint was complete response (CR). Patients with locally/regionally advanced cutaneous SCC deemed unsuitable for surgery received definitive radiotherapy (RT; 70 Gy in 35fractions) and concurrent weekly platinum-based chemotherapy (cisplatin 40 mg/m2 or carboplatin area under the curve 2).Twenty-one patients were enrolled in this study. Eighteen patients had a locally advanced primary or nodal disease in the head and neck region with 66% having stage IV nonmetastatic disease. Of 19 evaluable patients, 10 achieved a CR to definitive CRT with 2 further patients rendered disease-free by salvage surgery for an overall CR of 63%.This is the only prospective series of CRT for cutaneous SCC. A high CR rate was documented in patients with locoregional advanced disease who were unable to undergo surgery. © 2016 Wiley Periodicals, Inc. Head Neck 39: 679-683, 2017.

Relapsed glioblastoma multiforme (GBM) responds poorly to standard therapies. Vascular endothelial growth factor (VEGF) is implicated in the development of GBM and the anti-VEGF monoclonal antibody bevacizumab has shown early clinical promise against malignant glioma. We treated six patients with recurrent GBM using bevacizumab combined with carboplatin and etoposide chemotherapy (ACE regimen). Toxicity was that expected for carboplatin and etoposide alone, except for an ischemic stroke in one patient. We observed partial responses in five patients and one responding patient developed extensive tumour necrosis after 2 cycles of treatment. Median progression-free and overall survival was 19 and 29.9 weeks, respectively. Four responding patients developed recurrence, which was characterized by markedly less peri-tumoral edema, mass effect and necrosis compared with tumours at baseline. Two patients developed local extracranial extension. In conclusion, ACE was active in recurrent GBM and was mostly well tolerated.

A LETTER IN RESPONSE TO: Lakhanpal R, Stuart-Harris R, Chan A et al. Docetaxel and cyclophosphamide as adjuvant chemotherapy for early breast cancer: primary prophylaxis with G-CSF is required. Breast Cancer Manage. 2(5), 367–374 (2013).

In adults, nesidioblastosis is a very infrequent condition and a rare cause of symptomatic presentations. The diagnosis of nesidioblastosis may be difficult with functional and anatomical imaging modalities. "Slight focal" pancreatic abnormalities using (111)In-pentetreotide imaging has been reported in patients with hyperinsulinaemic hypoglycaemia, confirmed histologically as nesidioblastosis. We describe a 60-year-old man who presented with a 1-year history of intermittent faecal urgency and refractory diarrhoea, non-specific laboratory results, negative imaging results (CT, MRI and EUS), a FNA biopsy that was inconclusive, but suggested an endocrine cell neoplasm, and a (111)In-pentetreotide scan that showed a moderately intense focal uptake clearly localised to the pancreatic head on a low-dose fusion CT. The histopathology of the specimen confirmed the diagnosis of nesidioblastosis.

A 38-year-old woman with recurrent metastatic cervical adenocarcinoma developed innumerable bilateral solid and cavitating pulmonary metastatic nodules. After chemotherapy with paclitaxel and carboplatin, all these nodules regressed to air filled cystic structures with imperceptible walls, pneumatoceles. Immunocompromised patients require close monitoring for development of these as they may be complicated by secondary infection, pneumothorax formation or develop into a tension pneumatocele.

Purpose CYT997 is a novel microtubule inhibitor and vascular disrupting agent. This phase I trial examined the safety, tolerability, pharmacokinetics and vascular-disrupting effects of orally-administered CYT997. Experimental design We performed a phase I accelerated dose-escalation study of CYT997 given orally once every 2 to 3 weeks in patients with advanced solid tumours. Vascular disruption was assessed by measurement of plasma von Willebrand factor (vWF) levels and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results A total of 56 doses were administered to 21 patients over 8 dose levels (15–164 mg/m2). Grade 3 fatigue and grade 3 hypoxia were dose limiting. Oral bioavailability was observed with approximate linear pharmacokinetics over the 11-fold dose range. At doses of 84 mg/m2 and above, plasma vWF levels increased above baseline and DCE-MRI scans showed reductions in tumour Ktrans in some patients. Conclusions CYT997 is orally bioavailable. The 118 mg/m2 dose level should be used to guide dosing in future studies.

The ability of solid tumours to promote a pathological neovasculature is essential to their survival, growth and metastasis. Therefore, agents that damage or inhibit the formation of tumour blood vessels have the potential for significant anti-cancer activity (Folkman, 2002). It is critical that these interventions selectively target tumour blood vessels so that vascular toxicity to normal tissues is limited. Encouragingly, there are major biological differences between the immature disorganised microvasculature of malignant tumours and normal microvessel networks, and these differences provide the basis for therapeutic selectivity (Hinnen and Eskens, 2007). One class of vascular-targeting anti-cancer agents is the vascular-disrupting agents (VDAs). These drugs selectively disrupt endothelial cells within the tumour microvasculature, resulting in rapid shutdown of tumour blood flow (Hinnen and Eskens, 2007; Tozer et al, 2008). In animal models, this typically results in necrosis of the central region of the tumour, with a thin peripheral rim of surviving tumour cells that are presumably supplied by vessels in the adjacent normal tissue. Agents in this class include combretastatin A4 phosphate, 5,6-dimethylxanthenone-4-acetic acid, ZD6126 and others (Rustin et al, 2003; Stevenson et al, 2003; Beerepoot et al, 2006; McKeage et al, 2006). Although different mechanisms of action are operative, some VDA are tubulin-interactive small molecules that selectively inhibit microtubule polymerisation in endothelial cells (Tozer et al, 2008; Schwartz, 2009). Tumour endothelium is dependent on its microtubule cytoskeleton for structural and functional integrity, and disruption of microtubules can trigger a series of changes that shutdown blood flow in the tumour microvasculature (Hinnen and Eskens, 2007). Several VDA are currently in clinical development and some have shown clinical anti-cancer efficacy (Dowlati et al, 2002; McKeage et al, 2008). CYT997 is a synthetic small molecule that inhibits tubulin polymerisation, disrupts cellular microtubules and demonstrates potent cytotoxic activity against tumour cell lines in vitro (Burns et al, 2009b). It also showed significant vascular-disrupting activity in preclinical tumour models (Burns et al, 2009a). CYT997 is orally bioavailable and repeat-dose animal toxicology studies have evaluated both intravenous (i.v.) and oral schedules. Common toxicities included hypocellularity of spleen, thymus and bone marrow, leucopenia and mucosal hemorrhage and ulceration in the gastrointestinal tract. Mild bradycardia was observed at higher doses, but there were no other cardiovascular or neurological toxicities (Cytopia Research Pty Ltd, 2009). We now report the results of a phase I dose-finding study of CYT997 administered by continuous 24-h i.v. infusion in patients with refractory advanced cancer. Pharmacodynamic (PD) evaluations of vascular-disrupting activity were performed, including measurement of plasma von Willebrand factor (vWF) and circulating endothelial cells (CECs), and assessment of the tumour microvasculature with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We also evaluated plasma levels of caspase-cleaved cytokeratin-18 (CK-18) as a surrogate marker of tumour apoptosis.

8538 Background: Our state, Queensland, Australia, has the highest rate of cutaneous squamous cell cancer (SCC) in the world. Spread to regional lymph nodes or more distant sites occurs in 5-10%. A proportion of patients can not undergo surgical resection but complete response rates with radiotherapy alone are low. This led to the hypothesis that combined chemoradiation (CRT) may be of benefit. We decided to document the outcomes of concurrent chemoradiation by means of a prospective trial. Methods: This was a single arm, phase II study with planned sample size 30 patients. The primary endpoint was complete response rate (CRR), estimate 60%. Patients with locally/regionally advanced (non-metastatic) cutaneous SCC deemed unresectable or unsuitable for surgery by consensus of the multidisciplinary Head and Neck Cancer Clinic, with measurable disease, aged over 18, performance status 0-2, received definitive radiotherapy (XRT) (70Gy in 35#) and concurrent weekly platinum based chemotherapy (CT) (cisplatin 40mg/m2 or carboplatin AUC 2). Results: 14 patients were enrolled (Feb 2008-June 2011), median age 66 (48-84), 64% ECOG PS 0, 64% stage IV, 57% nodal disease only. Cisplatin/carboplatin was administered in 64%/36% respectively. 42% received all planned CT while 58% had 1 or 2 weeks omitted. 2 patients had dose reductions. XRT was completed as planned in 93%. The CRR was 57% (8/14) at analysis in December 2011 (median follow-up 13.5m). 2 further patients with partial response (PR) achieved CR after undergoing salvage surgery. Six (43%) patients had a PR; 4(29%) did not receive surgery and later progressed. Median overall survival was not reached, with 3 year survival 54%. The most frequent toxicities were dermatitis, mucositis, thrombocytopenia, nausea, anaemia, dysphagia. 28% had grade 3/4 toxicity, mainly cytopenias, infection, dehydration and nausea. Conclusions: This is the only prospective series of CRT for cutaneous squamous cell cancer. A high complete response rate was documented in patients with loco-regionally advanced disease and multiple co-morbidities, with acceptable toxicity, making this a reasonable alternative for patients unable to undergo surgery.

3568 Background: CYT997 is a novel, small-molecule vascular disrupting agent which binds tubulin and inhibits microtubule assembly. The compound demonstrates potent antitumour and vascular-disrupting activity in preclinical models. A phase I study of CYT997 given by intravenous infusion showed favourable safety and tolerability, pharmacokinetics and preliminary evidence of pharmacodynamic activity. Unlike most other VDAs, CYT997 is orally available and a phase I dose-ranging study with oral capsule dosing is underway. Methods: CYT997 was administered orally every 2 weeks to patients with advanced solid tumours. Doses were escalated using an accelerated phase I design to cohort 6 and thereafter with a standard 3+3 design. Pharmacodynamic effects on tumour vasculature were assessed with DCE-MRI scans, circulating endothelial cell (CEC) assays and von Willebrand factor (vWF) plasma levels. Results: 21 patients (M/F: 16/5; median age 63, range 48–77) have been treated on study. A total of 56 cycles of CYT997 have been administered (median 2/patient, range 1–7) over 8 dose levels (15 - 164 mg/m2). Doses up to 118 mg/m2 were well tolerated. However, dose-limiting toxicities were observed at 164 mg/m2, consisting of grade 3 hypoxia in one patient and grade 3–4 asthenia in two patients. The grade 3 hypoxia was reversible. PK profiles revealed favourable oral absorption which was generally dose-linear. DCE-MRI assessments indicating significant changes in tumour Ktrans values consistent with vascular disruption were observed in 6 of 10 currently evaluated patients. No objective tumour responses were seen; however, disease stabilisation for six weeks or greater was observed in 13 patients. vWf and CEC analysis is currently ongoing. Conclusions: Orally-administered CYT997 is well tolerated at doses associated with vascular targeting activity. Moreover, its good oral bioavailability suggests the potential for novel administration schedules, including metronomic dosing. [Table: see text]

Background The role of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scanning in operable pancreas cancer is unclear. We, therefore, wanted to investigate the impact of PET/CT on management, by incorporating it into routine work‐up. Methods This was a single‐institution prospective study. Patients with suspected and potentially operable pancreas, distal bile duct or ampullary carcinomas underwent PET/CT in addition to routine work‐up. The frequency that PET/CT changed the treatment plan or prompted other investigations was determined. The distribution of standard uptake values (SUV) among primary tumours, and adjacent to biliary stents was characterised. Results Fifty‐six patients were recruited. The surgical plan was abandoned in 9 (16%; 95% CI: 6–26) patients as a result of PET/CT identified metastases. In four patients, metastases were missed and seven were inoperable at surgery, not predicted by PET/CT. Unexpected FDG uptake resulted in seven additional investigations, of which two were useful. Among primary pancreatic cancers, a median SUV was 4.9 (range 2–12.1). SUV was highest around the biliary stent in 17 out of 28 cases. PET/CT detected metastases in five patients whose primary pancreatic tumours demonstrated mild to moderate avidity (SUV Conclusions PET/CT in potentially operable pancreas cancer has limitations. However, as a result of its ability to detect metastases, PET/CT scanning is a useful tool in the selection of such patients for surgery.

3504 Background: CYT997 binds α-tubulin, inhibits microtubule assembly and demonstrates potent anti-tumour and vascular- disrupting activity in preclinical models. A phase I dose-finding study in p...