Role of IL-17 and IL-22 in autoimmunity and cancer.

The dysregulation of inflammatory cytokines can cause a variety of diseases, such as autoimmunity and cancer. Since their identification in 2005, Th17 cells and its signature cytokine IL-17, have been implicated in the pathogenesis of autoimmune diseases such as psoriasis and rheumatoid arthritis (RA), and inflammatory associated cancers such as colorectal carcinoma (CRC). Recently, IL-22 a Th17 related cytokine has been shown to be pathogenic in psoriasis and RA. In this review, we will summarize the biological functions of IL-17 and IL-22, their role in autoimmune diseases and briefly review results from clinical trials targeting IL-17 or its receptor for the treatment of autoimmune diseases. Next, we will discuss pre-clinical and clinical data supporting the rationale of targeting other cytokines implicated in the Th17/IL-17 pathway, such as IL-22 and IL-23. Finally, we discuss the role of IL-17, and in particularly IL-22 in tumour immunity and possible therapeutic interventions.

A simple model for transit dosimetry based on a water equivalent EPID.

PURPOSE: The aim of this study was to demonstrate a new model for implementing a transit dosimetry system as a means of in vivo dose verification with a water equivalent electronic portal imaging device (WE-EPID) and a conventional treatment planning system (TPS). METHOD AND MATERIALS: A standard amorphous silicon (a-Si) EPID was modified to a WE-EPID configuration by replacing the metal-plate/phosphor screen situated above the photodiode detector with a 3 cm thick water equivalent plastic x ray converter material. A clinical TPS was used to calculate dose to the WE-EPID in its conventional EPID position behind the phantom/patient. The "extended phantom" concept was used to facilitate dose calculation at the EPID position, which is outside the CT field of view (FOV). The CT images were manipulated from 512 × 512 into 1024 × 1024 and padded pixels were assigned the density of air before importing to the TPS. The virtual WE-EPID was added as an RT structure of water density at the EPID plane. The accuracy of TPS dose calculations at the EPID plane in transit geometry was first evaluated for different field sizes and thickness of object in the beam by comparison with the dose measured using a 2D ion chamber array (ICA) and the WE-EPID. Following basic dose response tests, clinical fields including direct single fields (open and wedged) and modulated fields (integrated or control point by control point doses for VMAT) were measured for 6 MV photons with varying of solid water thickness or an anthropomorphic phantom present in beam. The EPID images were corrected for dark signal and pixel sensitivity and converted to dose using a single dose calibration factor. The 2D dose evaluation was conducted using 3%/3 and 2%/2 mm gamma-index criteria. RESULTS: The measured dose-response with the ICA and WE-EPID for all basic dose-response tests agreed with TPS dose calculations to within 1.5%. The maximum difference in dose profiles for the largest measured field size of 25 × 25 cm2 was 2.5%. Gamma evaluation showed at least 94% (3%/3 mm criteria) and 90% (2%/2 mm) agreement in both integrated and control-point doses for all clinical fields acquired by the WE-EPID and ICA when compared with TPS-calculated portal dose images. CONCLUSION: A new approach to transit dose verification has been demonstrated utilizing a water equivalent EPID and a commercial TPS. The accuracy of dose calculations at the EPID plane using a commercial TPS beam model was experimentally confirmed. The model proposed in this study provides an accurate method to directly verify doses delivered during treatment without the additional uncertainties inherent in modelling the complex dose-response of standard EPIDs.

Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.

PURPOSE: Measurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. METHODS: VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. RESULTS: Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The majority of errors (58/59 for institution 1, 54/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.

Optimisation of the imaging and dosimetric characteristics of an electronic portal imaging device employing plastic scintillating fibres using Monte Carlo simulations.

A Monte Carlo model of a novel electronic portal imaging device (EPID) has been developed using Geant4 and its performance for imaging and dosimetry applications in radiotherapy has been characterised. The EPID geometry is based on a physical prototype under ongoing investigation and comprises an array of plastic scintillating fibres in place of the metal plate/phosphor screen in standard EPIDs. Geometrical and optical transport parameters were varied to investigate their impact on imaging and dosimetry performance. Detection efficiency was most sensitive to variations in fibre length, achieving a peak value of 36% at 50 mm using 400 keV x-rays for the lengths considered. Increases in efficiency for longer fibres were partially offset by reductions in sensitivity. Removing the extra-mural absorber surrounding individual fibres severely decreased the modulation transfer function (MTF), highlighting its importance in maximising spatial resolution. Field size response and relative dose profile simulations demonstrated a water-equivalent dose response and thus the prototype's suitability for dosimetry applications. Element-to-element mismatch between scintillating fibres and underlying photodiode pixels resulted in a reduced MTF for high spatial frequencies and quasi-periodic variations in dose profile response. This effect is eliminated when fibres are precisely matched to underlying pixels. Simulations strongly suggest that with further optimisation, this prototype EPID may be capable of simultaneous imaging and dosimetry in radiotherapy.

Single arc volumetric modulated arc therapy for complex brain gliomas: is there an advantage as compared to intensity modulated radiotherapy or by adding a partial arc?

The objective of this study was to determine if volumetric modulated arc therapy (VMAT) offers advantages over intensity modulated radiotherapy (IMRT) for complex brain gliomas and evaluate the role of an additional partial arc. Twelve patients with glioma involving critical organs at risk (OAR) were selected [six low grade brainstem glioma (BG) and six glioblastoma (GB) cases]. BGs were prescribed 54 Gy/30 fractions (frx), and GB treated to 50 Gy/30 frx to a lower dose PTV (PTV50) with a simultaneous integrated boost delivering a total dose of 60 Gy/30 frx to a higher dose PTV (PTV60). VMAT was planned with a single arc (VMAT1) and with an additional coplanar partial arc spanning 90° (VMAT2). We observed VMATI improving the PTV equivalent uniform dose (EUD) for BG cases (p=0.027), improving the V95 for the PTV50 in GB cases (p=0.026) and resulting in more conformal GB plans (p=0.008) as compare to IMRT. However, for the GB PTV60, IMRT achieved favorable V95 over VMAT1 and VMAT2 (0.0046 and 0.008, respectively). The GB total integral dose (ID) was significantly lower with VMAT1 and VMAT2 (p=0.049 and p=0.006, respectively). Both VMAT1 and VMAT2 reduced the ID, however, only at the 5 Gy threshold for BG cases (p=0.011 and 0.005, respectively). VMAT achieved a lower spinal cord maximum dose and EUD for BG cases and higher optic nerve doses, otherwise no significant differences were observed. VMAT1 yielded the fastest treatment times and least MU. We conclude that VMAT offers faster treatment delivery for complex brain tumors while maintaining similar dosimetric qualities to IMRT. Selective dosimetric advantages in terms of spinal cord sparing and lowering the ID are observed favoring the use of an additional coplanar partial arc.