Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. MATERIALS AND METHODS: During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. RESULTS: An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. CONCLUSION: IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283]

BACKGROUND: Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. METHODS/DESIGN: The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment. DISCUSSION: The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life

Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers

Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release

Biomechanical advantages of dual over single iliac screws in lumbo-iliac fixation construct

The development of iliac screws has provided a markedly easier way for spino-pelvic instrumentation than the classical Galveston technique. However, high rates of iliac screw loosening and breakage are usually reported, especially in cases where bilateral single iliac screws are used. Therefore, there is a need for exploring more stable iliac fixation techniques. Thus, the objective of this study was to compare the biomechanical effects of bilateral single and dual iliac screws on the stability of L3-iliac fixation construct under total sacrectomy condition. In this study, L2-pelvic specimens were harvested from seven fresh human cadavers. After biomechanically testing the intact state simulated by L3-L5 pedicle screw fixation, destabilization was introduced by total sacrectomy. Upon destabilization, L3-iliac screw-rod reconstructions were performed by four different techniques as follows: (1) bilateral single short iliac screws (Single-Short); (2) bilateral single long iliac screws (Single-Long); (3) bilateral dual short iliac screws, placed in the upper and lower iliac columns (Dual-UL); and (4) bilateral dual short iliac screws, all placed in the lower iliac column (Dual-Lower). These four iliac screw fixation techniques were sequentially preformed in the same specimen, and the lengths of the short and long iliac screws were 70 and 130 mm, respectively. Biomechanical testing was performed on a material testing machine under 800 N compression and 7 Nm torsion loading modes to evaluate the construct stiffness. In compression, the stiffness of the L3-iliac fixation constructs of Single-Short, Single-Long, Dual-UL, and Dual-Lower techniques were 73, 76, 98, and 108% of the intact state, respectively. No significant differences were detected between Single-Short and Single-Long (P = 0.589) techniques. However, the compressive stiffness of these two techniques was significantly lower than the intact state, and the Dual-UL and Dual-Lower techniques (P < 0.05). There was no statistical difference between the intact condition and the Dual-Lower technique (P = 0.109). Interestingly, Dual-Lower exhibited notably higher compressive stiffness than Dual-UL (+10.3%, P = 0.049). In torsion, the stiffness of Single-Short, Single-Long, Dual-UL, and Dual-Lower techniques were 72, 79, 105, and 109% of the intact condition, respectively. No significant differences were detected between Single-Short and Single-Long techniques (P = 0.338), and also among Dual-UL, Dual-lower techniques, and the intact state (P > 0.05). However, Single-Short and Single-Long techniques provided markedly lower construct torsional stiffness than the other three groups (P < 0.05). For lumbo-illiac reconstruction after total sacrectomy, even the use of bilateral single, long iliac screws do not help in restoring the local stability to the intact condition. However, dual iliac screws provide much higher construct stability than single iliac screw techniques. Therefore, dual iliac screw technique should be preferred for treating the unstable situation caused by total sacrectomy