Craig A. Elith

Engagement of Variant CD44 Confers Resistance to Anti-Integrin Antibody-Mediated Apoptosis in a Colon Carcinoma Cell Line

The LIM 1863 colon carcinoma cell line grows as structured organoids around a central lumen, and we have previously demonstrated that the three-dimensional arrangement protects the individual cells from apoptosis induced by an anti-alpha v integrin antibody, 23C6 (Bates et al., 1994). Here we show that the intercellular forces which drive spheroid formation can be overcome by exposure of the cells to a collagen substrate, or more specifically through ligation of the CD44 receptor by a monoclonal antibody. Binding to immobilized anti-CD44 antibody induced a monolayer morphology which is accompanied by fibronectin production and secretion, and expression of the integrin alpha v beta 6. Significantly, the cells of the monolayer acquired resistance to 23C6 antibody-mediated apoptosis over time and this property was sustained even after removal from the monolayer. We provide data to show that this resistance is not dependent on monolayer morphology, constant engagement of the CD44 receptor, loss of the 23C6 antigen, or elevation of Bcl-2 or Bcl-XL protein. The CD44 expressed by LIM 1863 is shown to be the metastatic variant of the molecule therefore these results provide a possible explanation for the selective advantages conferred by expression of this variant for metastasizing colon cancer cells. Overall, the findings of this study support a model for the development of malignancy through the production of specific survival and growth signals as a direct consequence of a signaling event induced by stimulation of an epithelial variant of CD44.

A retrospective planning analysis comparing intensity modulated radiation therapy (IMRT) to volumetric modulated arc therapy (VMAT) using two optimization algorithms for the treatment of early‐stage prostate cancer

The primary aim of this study is to compare intensity modulated radiation therapy (IMRT) to volumetric modulated arc therapy (VMAT) for the radical treatment of prostate cancer using version 10.0 (v10.0) of Varian Medical Systems, RapidArc radiation oncology system. Particular focus was placed on plan quality and the implications on departmental resources. The secondary objective was to compare the results in v10.0 to the preceding version 8.6 (v8.6).

The quality assurance of volumetric modulated arc therapy (VMAT) plans for early stage prostate cancer: a technical note

As radiation therapy transitions from intensity modulated radiation therapy (IMRT) to volumetric modulated arc therapy (VMAT) it is important to consider the quality assurance (QA) of VMAT plans in light of what has previously been learned and developed in IMRT QA. This technical note assesses if IMRT based plan QA software, which has reduced the need in IMRT for phantom dose measurements on the linear accelerator, can be incorporated into VMAT QA processes. Twenty prostate cases were retrospectively planned using VMAT with one arc to deliver a prescription of 74 Gy in 37 fractions. A plan QA was performed using both IMSure (version 3.3), a software‐based IMRT QA program, and ArcCHECK (version 6.2.3.5713), a phantom‐based VMAT QA tool. Outcomes assessed included the time needed to perform the QA of both the IMSure and ArcCHECK QA methods, and agreement between planned dose and QA measured dose. On average per case, the ArcCHECK technique needed 31.5 min to perform the VMAT plan QA, while IMSure required 3.5 min to perform the same QA. All 20 cases passed dosimetric QA using ArcCHECK. However, using IMSure, three cases failed dosimetric QA using the departments existing IMRT QA criteria. This research has demonstrated that the IMRT QA software IMSure may be incorporated into the QA of VMAT plans, however the criteria to assess the dosimetry of the VMAT plans may need to be different to that for IMRT cases. The implication of this research for radiation therapists is to be critically aware of the differences between the plan QA requirements and methods for IMRT and those required for VMAT.

Template-based breast IMRT planning for increased workload efficiency

BackgroundTo be less resource intensive, we developed a template-based breast IMRT technique (TB-IMRT). This study aims to compare resources and dose distribution between TB-IMRT and conventional breast radiation (CBR).MethodsTwenty patients with early stage breast cancer were planned using CBR and TB-IMRT. Time to plan, coverage of volumes, dose to critical structures and treatment times were evaluated for CBR and TB-IMRT. Two sided-paired t tests were used.ResultsTB- IMRT planning time was less than CBR (14.0 vs 39.0 min, p < 0.001). Fifteen patients with CBR needed 18 MV, and 11 of these were planned successfully with TB-IMRT using 6 MV. TB-IMRT provided better homogeneity index (0.096 vs 0.124, p < 0.001) and conformity index (0.68 vs 0.59, p = 0.003). Dose to critical structures were comparable between TB-IMRT and CBR, and treatment times were also similar (6.0 vs 7.8 min, p = 0.13).ConclusionsTB- IMRT provides reduction of planning time and minimizes the use of high energy beams, while providing similar treatment times and equal plans compared to CBR. This technique permits efficient use of resources with a low learning curve, and can be done with existing equipment and personnel.

Comparing four volumetric modulated arc therapy beam arrangements for the treatment of early-stage prostate cancer

This study compared four different volumetric modulated arc therapy (VMAT) beam arrangements for the treatment of early‐stage prostate cancer examining plan quality and the impact on a radiotherapy departments resources.

A comparison of the acute toxicities using moderate hypo-fractionated intensity-modulated radiation therapy or volumetric modulated arc therapy for the treatment of early-stage prostate cancer

Aim This study compared the acute toxicities reported during radiotherapy treatment using either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) to deliver a moderate hypo-fractionated treatment for early-stage prostate cancer. Material and methods Acute toxicities are routinely reported at the clinical site for all patients using the Common Terminology Criteria for Adverse Events. Toxicity assessment is performed on day 1 of treatment, then once weekly thereafter. The recorded toxicities of 40 cases treated with five-field IMRT, and 32 cases treated using VMAT were retrospectively compared. All cases were prescribed 73·68 Gy in 28 fractions. Eight symptoms were assessed; diarrhoea, proctitis, fatigue, pain, dermatitis, urinary frequency, urinary retention and urinary tract pain. Results In terms of the overall toxicity recorded, VMAT was shown to reduce the toxicities of dermatitis, fatigue, pain and urinary frequency ( p Findings The research reported here is one of the first publications to demonstrate that VMAT is associated with decreased toxicities compared with IMRT for the treatment of early-stage prostate cancer.