Fiducial markers: can the urologist do better?

INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy. METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging. CONCLUSION: This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.

Volumetric arc therapy: A viable option for right-sided breast with comprehensive regional nodal irradiation in conjunction with deep inspiration breath hold.

PURPOSE: Deep inspiration breath hold (DIBH) is an innovative technique routinely used for left-sided breast radiotherapy to significantly reduce harmful dose to the heart and ipsilateral lung. Currently, there is scant literature exploring DIBH for right-sided whole breast and regional nodal irradiation (WB & RNI). The purpose of this study is to examine if DIBH produces a clinically significant reduction in organ at risk (OAR) dose for right-sided WB + RNI, whilst comparatively analysing the use of volumetric arc therapy (VMAT) versus tangential inverse modulated radiotherapy (t-IMRT). METHODS AND MATERIALS: Ten patients, previously treated for left sided breast cancer (with a FB and DIBH CT scan), were selected from our database to be retrospectively replanned to the right breast and nodal regions. Planning target volumes (PTV) were marked to include the whole right breast and regional nodes, encompassing the supraclavicular fossa (SCF) and internal mammary nodes (IMN). PTVs and OARs were contoured on the Pinnacle workstation according to the Radiation Therapy Oncology Group (RTOG) guidelines. VMAT and t-IMRT plans were generated to a prescribed dose of 50 Gy in 25 fractions on both the DIBH and FB data sets for dosimetric analysis. RESULTS: Coverage of the right breast (mean, D95%) and SCF (D95%) were significantly improved with VMAT in comparison to t-IMRT, with no statistically significant variation on the IMN PTV (D95%). The use of DIBH did not impact PTV coverage compared with FB. VMAT reduced dose to the ipsilateral lung (mean, V20Gy), combined lungs (mean, V20Gy) and liver (D2cc); conversely dose to the heart (mean), left lung (mean, V5Gy) and contralateral breast (mean) were increased. For both techniques DIBH significantly improved dose to OARs including the ipsilateral lung (mean, V20Gy, V5Gy), total lung (mean, V20Gy), heart (mean, V25Gy) and liver (D2cc) when compared to FB. CONCLUSION: DIBH could be considered for patients treated with right-sided WB and RNI due to a significant decrease in heart, ipsilateral lung, total lung and liver doses. VMAT significantly improves PTV coverage over t-IMRT whilst reducing dose to the ipsilateral lung and liver, albeit to the detriment of the left lung, contralateral breast and heart. The increase in heart dose can be mitigated by the use of DIBH. We recommend if VMAT is utilised for superior target volume coverage, DIBH should also be implemented to reduce OAR toxicity. RÉSUMÉ:   BUT: La retenue respiratoire profonde (DIBH) est une technique innovante couramment utilisée pour la radiothérapie du cÔté gauche du sein afin de réduire de manière significative la dose nocive pour le cŒur et le poumon ipsilatéral (13-15). Actuellement, il existe peu d'ouvrages sur la DIBH pour l'irradiation du sein entier du cÔté droit et des nodules régionaux (WB+RNI). L'objectif de cette étude est d'examiner si la DIBH produit une réduction cliniquement significative de la dose d'organe à risque (OAR) pour la WB+RNI du cÔté droit, tout en analysant comparativement l'utilisation de l'arcthérapie volumétrique (VMAT) par rapport à la radiothérapie par modulation d'intensité tangentielle (t-IMRT). MéTHODOLOGIE ET MATéRIEL: Dix scans tomodensitométriques avec un ensemble de données DIBH et de respiration libre (FB) ont été sélectionnés de manière rétrospective. Les volumes cibles de planification (PTV) ont été marqués pour inclure le sein droit entier et les ganglions régionaux, englobant la fosse supraclaviculaire (SCF) et les ganglions mammaires internes (IMN). Les PTV et les OAR ont été définis sur la station de travail Pinnacle conformément aux directives du groupe de radiothérapie oncologique (RTOG) (17). Les plans t-IMRT et VMAT ont été générés pour une dose prescrite de 50Gy en 25 fractions sur les ensembles de données DIBH et FB pour l'analyse dosimétrique. RéSULTATS: La couverture du sein droit (moyenne, D95%) et du SCF (D95%) a été significativement améliorée avec la VMAT par rapport à la t-IMRT, sans variation statistiquement significative sur la PTV IMN (D95%). L'utilisation de la DIBH n'a pas eu d'impact sur la couverture du PTV par rapport à la FB. La VMAT a réduit la dose dans le poumon ipsilatéral (moyenne, V20Gy), les poumons combinés (moyenne, V20Gy) et le foie (D2cc) ; à l'inverse, la dose dans le cŒur (moyenne), le poumon gauche (moyenne, V5Gy) et le sein controlatéral (moyenne) a été augmentée. Pour les deux techniques, la DIBH a amélioré de manière significative la dose aux OAR, y compris le poumon ipsilatéral (moyenne, V20Gy, V5Gy), le poumon total (moyenne, V20Gy), le cŒur (moyenne, V25Gy) et le foie (D2cc), par rapport à la respiration libre. CONCLUSION: La DIBH pourrait être envisagé pour les patients traités par WB+RNI du cÔté droit en raison d'une diminution significative des doses dans le cŒur, le poumon ipsilatéral, le poumon total et le foie. La VMAT améliore considérablement la couverture de la PTV par rapport à la t-IMRT tout en réduisant la dose dans le poumon ipsilatéral et le foie, mais au détriment du poumon gauche, du sein controlatéral et du cŒur. L'augmentation de la dose au cŒur peut être atténuée par l'utilisation de la DIBH. Nous recommandons, si la VMAT est utilisée pour une couverture supérieure du volume cible, de mettre également en Œuvre la DIBH pour réduire la toxicité aux OAR.

Exploratory models comparing ethiodized oil-glue and gold fiducials for bladder radiotherapy image-guidance.

BACKGROUND AND PURPOSE: Image-guidance with fiducials has been shown to improve pelvic radiotherapy outcome. However, bladder fiducials using ethiodized oil (EO) alone can disperse widely, and gold causes Computed Tomography scan (CT) metal artifacts. The study's purpose was to investigate the ability to deliver EO-tissue glue fiducials and compare them to gold for bladder radiotherapy image guidance. MATERIALS AND METHODS: A fluid-filled porcine bladder model was used to assess the ability to cystoscopically inject visible EO glue fiducials into the submucosa. We then transferred the bladders into a porcine pelvis for imaging and compared them to gold fiducials using CT, Cone Beam CT (CBCT), and kilovoltage (KV) planar views. A tissue-equivalent phantom was utilized to analyze the CT number Hounsfield Unit (HU) characteristics and artifacts of the glue and gold fiducials. Percentile ranges and normal tissue voxel percentages of the subsequent CT number voxel histogram from a 2 cm sphere surrounding the fiducial was used to characterize the artifact. RESULTS: We successfully delivered all EO glue fiducials into the porcine bladders as discrete fiducials. They were well seen on CT, CBCT, and KV imaging. The glue fiducials had lower CT number values, but less CT number spread of the voxel percentile ranges consistent with the diminished contrast and less artifact than gold. The glue fiducial types had similar CT number characteristics. CONCLUSION: This study has shown that EO glue fiducials can be delivered with online visualization qualities comparable to gold fiducials without metal-related artifacts.

Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre.

PURPOSE: To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. METHODS AND MATERIALS: From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5-8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8-years post treatment. RESULTS: All patients completed radiotherapy without any treatment breaks. The 8-year risks of ≥ Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of ≥ Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. CONCLUSIONS: These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting.