Locoregional failure analysis in head-and-neck cancer patients treated with IMRT

PURPOSE: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions. PATIENTS AND METHODS: Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors' institution. Mean follow-up was 23.2 months (3-59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1-2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed. RESULTS: 2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed "in field". No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features. CONCLUSION: The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volume

Protective films on complex substrates of thermoplastic and cellular elastomers:Prospective applications to rubber, nylon and cork

Deposition of thin films is an appropriate methodology to enhance the performance of a material by modification of its surface, while keeping the properties of the bulk largely unaffected. However, a practical implementation becomes less straightforward when dealing with sensitive or complex substrates, for instance, those which cannot be subjected to harsh treatments, such as cleaning and etching, or extreme deposition conditions, like high temperatures, and ion impingement et cetera. This paper concentrates on deposition processing of complex substrates. In particular, it discusses the deposition of two types of protective coatings (diamond-like carbon (DLC) films against friction and wear, and TiO2 films against UV light) on three types of thermoplastic and cellular elastomers (rubber, nylon and cork). It is demonstrated that a successful protection of thermoplastic elastomers against wear with DLC films can be attained, after a thorough adaptation of the procedure to the characteristics of the specific substrate. In addition, the paper reports the very first depositions on a cellular elastomer like cork by vapor deposition methods, including Atomic Layer Deposition (ALD)

PET/CT Staging Followed by Intensity-Modulated Radiotherapy (IMRT) Improves Treatment Outcome of Locally Advanced Pharyngeal Carcinoma: a matched-pair comparison

BACKGROUND: Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. PATIENTS AND METHODS: Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls. RESULTS: PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). CONCLUSION: PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings

Uptake and localisation of mTHPC (Foscan®) and its14C-labelled form in normal and tumour tissues of the hamster squamous cell carcinoma model: a comparative study

The aim of this study was to evaluate the pharmacokinetics of meta(tetrahydroxyphenyl)chlorin (mTHPC) on different tissues of interest in a hamster tumour model and to confirm our earlier animal studies on semi-quantitative fluorescence microscopy. The results obtained by three different evaluation methods were compared: in vivo spectrofluorometry, ex vivo fluorescence microscopy and chemical extraction of 14C-labelled mTHPC. Following intracardiac injection of 0.5 mg kg−1 mTHPC, groups of five tumour-bearing animals were used for in situ light-induced fluorescence spectroscopy. Afterwards, the biopsies were taken and snap frozen for fluorescence microscopy. The presence of radioactivity in serum and tissues was determined after chemical digestion in scintillation fluid using a scintillation counter. For each analysed tissue, a good correlation was observed between the three evaluation methods. The highest fluorescence intensity and quantities of mTHPC were observed between 12 and 24 h in liver, kidney, serum, vascular endothelium and advanced neoplasia. The majority of mTHPC was found at around 48 h in smooth muscle and at 96 h in healthy cheek pouch mucosa and early malignant lesions. The lowest level of mTHPC was noted in striated muscle at all times. No selectivity in dye localisation was observed between early squamous cell carcinoma and healthy mucosa. Soon after the injection, a significant selectivity was noted for advanced squamous cell carcinoma as compared to healthy cheek pouch mucosa or striated muscle. A significant difference in mTHPC localisation and quantity was also observed between striated and smooth muscle during the first 48 h following the injection. Finally, this study demonstrated the usefulness of non-invasive in situ spectroscopic measurements to be performed systematically prior to photodynamic therapy as a real-time monitoring for each treated patient in order to individualise and adapt the light dosimetry and avoid over or under treatments

Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression

The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibitor (TFPI) and the underlying mechanisms were determined. Further, arterial thrombosis by photochemical injury of the common carotid artery, and TF expression in the murine endothelium were examined in C57BL/6 mice treated with ticagrelor or clopidogrel. Ticagrelor, but not CAM, reduced TNF-α-induced TF expression via proteasomal degradation and TF activity, independently of the P2Y12 receptor and the equilibrative nucleoside transporter 1 (ENT1), an additional target of ticagrelor. In C57BL/6 mice, ticagrelor prolonged time to arterial occlusion, compared with clopidogrel, despite comparable antiplatelet effects. In line with our in vitro results, ticagrelor, but not clopidogrel, reduced TF expression in the endothelium of murine arteries.Conclusion: Ticagrelor, unlike clopidogrel, exhibits endothelial-specific antithrombotic properties and blunts arterial thrombus formation. The additional antithrombotic properties displayed by ticagrelor may explain its greater efficacy in reducing thrombotic events in clinical trials. These findings may provide the basis for new indications for ticagrelor

Postoperative IMRT in head and neck cancer

BACKGROUND: Aim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres. Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2–48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60–70), delivered with doses per fraction of 2–2.3 Gy, respectively. RESULTS: 2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup. CONCLUSION: Surgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials

Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke

In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic strok