A Novel Liquid Fiducial Marker in Esophageal Cancer Image Guided Radiation Therapy: Technical Feasibility and Visibility on Imaging

PurposeTo assess the technical feasibility of injection, visibility on imaging modalities, and positional stability of a novel liquid fiducial marker (ie, BioXmark) for radiation therapy in patients with esophageal cancer.MethodsFirst, the visibility on imaging of different volumes of the liquid marker was analyzed ex vivo in porcine tissue (ie, on computed tomography [CT], cone beam CT (CBCT), and magnetic resonance imaging [MRI]). Next, for the in vivo part, the liquid fiducial markers were injected under endoscopic (ultrasound) guidance in 10 patients with curable esophageal cancer. The technical feasibility of the injection procedure and the clinical performance (ie, visibility and positional stability on imaging) were evaluated. Planning CT, daily CBCT, and serial MRI images (before, during, and after chemoradiation therapy in a subset of 3 patients) were acquired.ResultsEx vivo, the optimal volume for good visibility without artifacts was 0.1 mL per injected marker. In vivo, a total of 28 markers were injected in 10 patients (range, 0.025-0.1 mL). No adverse effects were identified. The first 2 cases (4 markers) were considered as learning cases. A total of 19 of 24 of the liquid markers (79%) were visible on CT, 3 of 4 (75%) on MRI, and 19 of 24 (79%) on the first CBCT. All markers with an injected volume of >0.05 mL were visible on the different imaging modalities. Positional stability analysis on CBCT identified no time trend during the radiation therapy course. No artifacts could be detected for liquid marker volumes of 0.05 and 0.025 mL in CT or CBCT.ConclusionsInjection of a liquid fiducial marker for esophageal cancer radiation therapy is technically feasible with no adverse events identified. Volumes of >0.05 mL have an appropriate visibility on CT, CBCT, and MRI, with an excellent positional stability. Liquid fiducial markers are therefore promising for use in image guided radiation therapy.     

Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

PurposeFiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT.MethodsAn institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers.ResultsWe identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present post-treatment imaging at a median of 107 days (range, 33-471 days) after implantation.ConclusionsEUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques.     

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy

PURPOSE: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. METHODS AND MATERIALS: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. RESULTS: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. CONCLUSIONS: Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.     

Deriving patient-specific planning target volume for partial bladder image guided radiation therapy

PurposeImage guided radiation therapy (IGRT) using bony anatomy for bladder cancer requires the use of large population-based planning target volume (PTV) margins to compensate for geometric uncertainties. This may result in a large volume of normal tissue being irradiated unnecessarily. Identification of the clinical target volume (CTV) is also a challenge during target delineation and treatment position verification. This study describes the use of lipiodol (Guerbet, US) and cone beam computed tomography (CBCT) in deriving patient-specific PTV (PS-PTV) for partial bladder IGRT.Methods and materialsTwelve patients underwent lipiodol injection into the bladder wall prior to radiation treatment. A PS-PTV was generated by the following: (1) Delineating partial bladder CTV (CTVpb) on 15 CBCTs; (2) registering the CBCTs with the planning CT image using lipiodol; (3) combining the 15 CTVpb to create an occupancy volume (OV); and (4) expanding the OV by 3 mm. Its efficacy in reducing irradiated volume and in providing coverage was assessed by comparing it with a 20-mm population-based PTV (popPTV) and using phase 2 CBCTs.ResultsThe median PS-PTV and popPTV (cm³) were 102 (range, 37-336) and 325 (range, 211-631), respectively. Median distance between the CTVpb and the PS-PTV edge (mm) were 6 superior, 6 right, 7 left, 7 anterior, 8 posterior, and 11 inferior. The absolute median reduction in the overlapping volume of rectum, small bowel, and large bowel were 0.3 cm³, 5.3 cm³, and 13.0 cm³, respectively. Despite large reductions in volume and margin compared with popPTV, PS-PTV achieved 100% target coverage.ConclusionsUsing lipiodol and CBCT to derive PS-PTV facilitated large reductions in the irradiated normal tissue volume without compromising target coverage.     

Triggered Imaging With Auto Beam Hold and Pre-/Posttreatment CBCT During Prostate SABR: Analysis of Time Efficiency,Target Coverage,and Normal Volume Changes

PurposeOur purpose was to investigate time efficiency and target coverage for prostate stereotactic ablative radiation therapy (SABR) using triggered imaging (TI) and auto beam hold.Methods and MaterialsA total of 20 patients were treated with volumetric modulated arc–based SABR. Treatment verification consisted of pre- and post-radiation therapy cone beam computed tomography (CBCT) with gold marker-based TI every 3 seconds. In case of ≥3 mm (deviation limit) displacement, the treatment was interrupted and imaging-based correction was performed. Beam interruptions, intrafractional shifts, and treatment times were recorded. Prostate, rectum, and bladder were delineated on each CBCT. Target coverage was evaluated by comparing the individual prostate delineations with 98% isodose contour volumes (% of the evaluated volumes exceeding the reference). Both inter- and intrafractional changes of bladder and rectal volumes were assessed.ResultsThe average overall treatment time (±standard deviation) was 18 ± 11 min, with a radiation delivery time of 6 ± 3 min if no intrafractional CBCT acquisitions were necessary (91% of fractions). On average, 1.2 beam interruptions per fraction were required with 0/1 correction in 71% of the fractions. The mean residual 3-dimensional shift was 1.6 mm, exceeding the deviation limit in 8%. In the case of intrafractional CBCT and/or ≥2 corrections the treatment time dramatically increased. The 98% isodose lines did not encompass the prostate in only 8/180 (4%) evaluations in 6 different patients, leading to a loss of D98 between 0.1%-6% as a worst case scenario. The bladder volumes showed significant increases during treatment (P < .01) while rectal volumes were stable.ConclusionsTime efficiency of TI + auto beam hold with 3 mm/3 sec threshold during prostate SABR is comparable with competitive techniques, resulting in minimal 3-dimensional residual errors with maintained target coverage. Technical developments are necessary to further reduce radiation delivery time. Use of CBCT allowed full control of rectal volumes, while bladder volumes showed significant increases over time.     

Clinical application of image-guided radiotherapy, IGRT (on the Varian OBI platform).

Image-guided radiation therapy (IGRT) can be used to measure and correct positional errors for target and critical structures immediately prior to or during treatment delivery. Some of the most recent available methods applied for target localization are: transabdominal ultrasound, implanted markers with in room MV or kV X-rays, optical surface tracking systems, implantable electromagnetic markers, in room CT such as kVCT on rail, kilovoltage or megavoltage cone-beam CT (CBCT) and helical megavoltage CT. The verification of the accurate treatment position in conjunction with detailed anatomical information before every fraction can be essential for the outcome of the treatment. In this paper we present the on-board imager (OBI, Varian Medical Systems, Palo Alto, CA) that has been in routine clinical use at the Karolinska University Hospital since June 2004. The OBI has been used for on-line set-up correction of prostate patients using internal gold markers. Displacements of these markers can be monitored radiographically during the treatment course and the registered marker shifts act as a surrogate for prostate motion. For this purpose, on-board kV-kV seems to be an ideal system in terms of image quality. The CBCT function of OBI was installed in March 2005 at our department. It focuses on localizing tumors based on internal anatomy, not just on the conventional external marks or tattoos. The CBCT system provides the capacity for soft tissue imaging in the treatment position and real-time radiographic monitoring during treatment delivery.     

Patient-specific PTV margins in radiotherapy for bladder cancer - A feasibility study using cone beam CT

Purpose

To assess the feasibility of using cone beam computed tomography (CBCT) to generate patient-specific PTV margins for bladder cancer patients treated with radiation therapy (RT).

Methods

Eleven patients underwent CT simulation and daily RT (full bladder and empty rectum). CBCT was done prior to each fraction, and the whole bladder was contoured off-line. For the first 15 CBCTs of each patient, the bladder was aligned with CT-simulation bladder (pBladder) to create an occupancy volume (OV). A 5 mm isotropic margin was added to OV (OV + 5). A measurement-based PTV (mPTV) was generated by measuring maximal displacement between pBladder and OV in six directions. OV, OV + 5, mPTV, and a standard PTV (2 cm isotropic margin) were compared for absolute and relative volume differences. Using the final 10 CBCT of each patient, the ability of each study volume to encompass the entire CBCT bladder was determined.

Results

161/165 CBCT images were of adequate quality for contouring. No daily trend in bladder volume variation was noted. The median absolute volumes (cm³) were: 221, 271, 426, 440, and 914 for pBladder, OV, OV + 5, mPTV, and standard PTV, respectively. The median ratios of the study volumes/pBladder were: 1.4 OV, 2.1 OV + 5, 2.4 mPTV, 4.1 standard PTV. OV + 5 was smaller than mPTV in 9 patients. There was considerable inter-patient variability in study volumes and no apparent association of the magnitude of margin expansion and pBladder. The bladder was encompassed in 69%, 99%, 99%, and 100% of the final 10 fractions by OV, OV + 5, mPTV, and standard PTV, respectively.

Conclusions

The use of daily CBCT to generate patient-specific PTV margins is feasible and results in a marked reduction in the irradiated volume compared to population-based margins. As daily bladder volume varied unpredictably with considerable differences between patients, these findings support the use of patient-specific PTV margin expansions for bladder radiotherapy.     

Addition of Iodinated Contrast to Rectal Hydrogel Spacer to Facilitate MRI-Independent Target Delineation and Treatment Planning for Prostate Cancer

PurposeHydrogel spacers reduce rectal dose toxicity during prostate cancer radiation therapy. Current products require magnetic resonance imaging (MRI) for visualization during treatment planning, but MRI incompatibility and cost have prompted alternatives using computed tomography (CT). This case series evaluates the addition of iodinated contrast to hydrogel as such an alternative.Methods and materialsThree patients underwent rectal hydrogel spacer placement with iodinated contrast modification. CT was performed within 1 hour of injection and again 1 week later. MRI was obtained at the time of the second CT. Hydrogel delineation was compared between CT and MRI and between paired CT scans.ResultsSpacer enhancement was visible on CT immediately after hydrogel placement (mean Hounsfield units, 122; range, 52-193) but not at the second CT 1 week later (mean Hounsfield units, 8; range, −8 to 29). Delineated spacer volume did not significantly differ between immediate postprocedure CT and MRI ≥1 week later in 2 patients (patient 1: 16.6 vs 15.5 cm³; patient 2: 12.6 vs 14.7 cm³; paired t-test, P = .81).ConclusionsCT visualization of rectal hydrogel admixed with contrast is feasible and allows delineation of interface with rectum/prostate.     

Feasibility of Same-Day Prostate Fiducial Markers,Perirectal Hydrogel Spacer Placement,and Computed Tomography and Magnetic Resonance Imaging Simulation for External Beam Radiation Therapy for Low-Risk and Intermediate-Risk Prostate Cancer

PurposeThe use of prostate fiducial markers and perirectal hydrogel spacers can reduce the acute and late toxic effects associated with prostate radiation therapy. These procedures are usually performed days to weeks before simulation during a separate clinic visit to ensure resolution of procedure-related inflammation. The purpose of this study was to assess whether same-day intraprostatic fiducial marker placement, perirectal hydrogel injection, and computed tomography (CT) and magnetic resonance imaging (MRI) simulation were feasible without adversely affecting hydrogel volume, perirectal spacing, or rectal dose. If feasible, performing these procedures on the same day as simulation would expedite the start of radiation therapy, improve patient convenience, and reduce costs.Methods and MaterialsTwenty-one patients with clinically localized prostate cancer who were enrolled on a prospective clinical trial (NCT01617161) underwent same-day marker placement, hydrogel injection, and CT and MRI simulation, then underwent T2 MRI verification scans 3 to 4 weeks later. The MRI scans were fused to the CT planning scans by clinical target volumes (CTVs) to generate comparison treatment plans (70 Gy in 28 fractions). Hydrogel volume and symmetry, perirectal spacing, CTV dose, and organ-at-risk dose were evaluated.ResultsVerification scans occurred a mean of 24.9 ± 4.6 days after simulation and 9.3 ± 4.9 days after treatment start. Prostate volume did not change between scans (median, 67.3 ± 22.1 cm³ vs 64.1 ± 21.8 cm³; P = .64). The median hydrogel change between simulation and verification was ⁻1.8% ± 4.5% (P = .27). No significant differences in perirectal spacing (midgland: 1.33 ± 0.45 cm vs 1.3 ± 0.7 cm; 1 cm superior: 1.25 ± 0.95 cm vs 1.43 ± 0.91 cm; 1 cm inferior: 1.16 ± 0.28 cm vs 1.41 ± 0.49 cm) were identified. No significant differences in rectal V66 (median 2.3 ± 2.18% vs 2.3 ± 2.28%; P = .99), V35 (median 14.79 ± 7.61 vs 14.67 ± 8.4; P = .73), or D1cc (65.7 ± 9.2 Gy vs 68.2 ± 9.0 Gy; P = .80) were found. All plans met CTV and organ-at-risk constraints.ConclusionSame-day placement of intraprostatic fiducial markers, perirectal hydrogel, and simulation scans was feasible and did not significantly affect hydrogel volume, position, CTV coverage, or rectal dose.     

Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

Introduction

While planning radiation therapy (RT) for a carcinoma of the urinary bladder (CaUB), the intra-fractional variation of the urinary bladder (UB) volume due to filling-up needs to be accounted for. This internal target volume (ITV) is obtained by adding internal margins (IM) to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility.

Methods

One patient with CaUB underwent simulation with the proposed ‘bladder protocol’. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T) was noted. Planning CT scans were performed after 20 min (T+20), 30 min (T+30) and 40 min (T+40). The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT) scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30.

Results

In total, there were 65 CBCT scans (36 pre- and 29 post-treatment). Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances.

Conclusions

The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.Key words: Radiation therapy, Carcinoma of the urinary bladder, Urinary bladder volume, Individualized internal target volume     

Inter- and intra-fractional bladder motion during radiotherapy for bladder cancer: A comparison of full and empty bladders

PurposeTo compare inter- and intra-fraction bladder volume variations and bladder wall motion during radiotherapy (RT) for bladder cancer with full and empty bladder protocols.Materials and methodsBladder volumes, filling rates and bladder wall movement were retrospectively analyzed for 24 patients with at least 4 sets of delineable pre and post treatment cone beam CT (CBCT)-scans. Eight patients were treated with an ‘empty bladder’ (EB) protocol and sixteen patients with a ‘full bladder’ (FB) protocol.Results24 planning CT-scans and 356 CBCT-scans (178 sets) were analyzed. The average time between pre and post irradiation CBCT was 8 min (range 6–18 min). Median filling rate was 1.94 ml/min and did not differ between EB and FB. Random variation in bladder volume and inter-fraction wall movement was slightly but not significantly larger for FB, whereas intra-fraction bladder wall movement was slightly but not significantly smaller for FB. The largest inter- and intra-fraction bladder wall movement was found in the cranial anterior direction.ConclusionEmpty and full bladder protocols show similar inter- and intra-fraction wall motion, and therefore treatment choices could be purely based on organ at risk criteria.     

Trimodal therapy for muscle-invasive bladder cancer

Introduction: Radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer. Organ-preserving surgical procedures have been established as alternatives to radical surgery for localized malignancies in other anatomic sites. Trimodal therapy consisting of radiation therapy, chemotherapy, and either transurethral resection of the bladder or partial cystectomy is an effective treatment for selected patients with muscle-invasive bladder cancer that allows for preservation of the urinary bladder.

Areas covered: This review provides an overview of the value of trimodal therapy in the treatment of muscle-invasive bladder cancer.

Expert commentary: Prerequisites for trimodal therapy for bladder cancer include: good bladder function, unifocal cT2 urothelial carcinoma of the bladder, and absence of hydronephrosis. Careful selection of patients and accurate assessment of the anatomic extent of the tumor is important for patient safety. The basis for successful trimodal therapy is complete transurethral resection of the tumor, followed by radiation therapy with concurrent radiosensitizing chemotherapy. Cystoscopic controls and follow-up biopsies should be performed at completion of adjuvant therapy or shortly after induction of trimodal therapy to identify nonresponders for whom salvage radical cystectomy may be indicated.     

Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer

BackgroundPre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer.Patients and methodsSeventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable.ResultsAn absolute lymphocyte count of 1.5 × 10⁹/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1–2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0–2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5–0.87; P = 0.003).ConclusionPre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.     

Inter‐observer variability of clinical target volume delineation for bladder cancer using CT and cone beam CT

To compare the image quality of cone beam CT (CBCT) with that of planning CT (pCT) scan, and quantify inter‐observer differences in therapeutic indices based on these scans prior to the introduction of an adaptive radiation therapy protocol for bladder cancer. Four consecutive patients were selected with muscle invasive bladder cancer receiving radical dose radiation therapy. Four radiation oncologists specializing in genitourinary malignancies contoured the clinical target volume (CTV) and rectum on both a pCT and a randomly chosen CBCT of the same patient. A conformity index (CI) for CTV and the rectum was determined for both pCT and CBCT. The maximal lateral, anterior, posterior, cranial and caudal extensions of the CTV for both CT and CBCT were determined for each observer. Variation in volumes of both the CTV and rectum for both pCT and were also compared using Varian Eclipse planning software (Varian Medical Systems, Palo Alto, CA, USA). Using pCT the mean CI for the CTV was 0.79; using CBCT the mean CI for the CTV was 0.75. For the rectum, the mean CI for using CT was 0.80 and for CBCT was 0.74. Greatest variation on CBCT CTV contours was seen in the supero‐inferior direction with variation up to 2.1 cm between different radiation oncologists. With the variation in CI for pCT and CBCT of the CTV and rectum (0.04 and 0.06 respectively), CBCT is not significantly inferior to the pCT in terms of inter‐observer contouring variability.     

Electromagnetic Transponder Localization and Real-Time Tracking for Prostate Cancer Radiation Therapy: Clinical Impact of Metallic Hip Prostheses

PurposeOur purpose was to assess the ability of electromagnetic transponders (EMTs) to localize and track movements in patients with prostate cancer (PCa) with metallic hip prostheses (MHPs) treated with curative radiation therapy (RT).Methods and MaterialsData sets of 8 PCa patients with MHPs (3 bilateral and 5 unilateral) treated between 2016 and 2018 with RT and EMT tracking were retrospectively assessed. The distances between the 3 EMTs (apex to left, left to right, right to apex) and the isocenter were calculated both on planning computed tomography (CT) and cone beam CT (CBCT) at the first treatment fraction and compared with data reported by Calypso. EMT position and treatment interruptions triggered by Calypso were analyzed for all evaluable treatment fractions (n = 120). Localization accuracy was quantified by recording the geometric residual value (expected limit ≤0.2 cm) at the RT setup.ResultsThe Calypso system was able to localize and track prostate position without any detectable interference from MHP. For every treatment fraction, the agreement between the CBCT images and Calypso guidance was optimal, with EMTs always within the defined tolerance (ie, CT-Calypso or CBCT-Calypso measured differences in inter-EMT distances within 0.3 cm). EMT to isocenter distances measured by Calypso reproduced CT data and were confirmed on CBCT scans. During RT, the EMT centroid exceeded the threshold 24 times (20% of all fractions): 5 times in the left-right, 15 times in the anteroposterior, and 4 times in the superoinferior directions. The largest motions recorded were in the anteroposterior axis: 0.6 cm anteriorly and 0.5 cm posteriorly in patients with unilateral and bilateral MHP, respectively.ConclusionsOur study represents the first clinical experience assessing the localization and tracking accuracy of Calypso EMTs during curative RT of patients with PCa with unilateral or bilateral MHP.     

Adaptive plan selection vs. re-optimisation in radiotherapy for bladder cancer: A dose accumulation comparison

Purpose

Patients with urinary bladder cancer are obvious candidates for adaptive radiotherapy (ART) due to large inter-fractional variation in bladder volumes. In this study we have compared the normal tissue sparing potential of two ART strategies: daily plan selection (PlanSelect) and daily plan re-optimisation (ReOpt).

Materials and methods

Seven patients with bladder cancer were included in the study. For the PlanSelect strategy, a patient-specific library of three plans was generated, and the most suitable plan based on the pre-treatment cone beam CT (CBCT) was selected. For the daily ReOpt strategy, plans were re-optimised based on the CBCT from each daily fraction. Bladder contours were propagated to the CBCT scan using deformable image registration (DIR). Accumulated dose distributions for the ART strategies as well as the non-adaptive RT were calculated.

Results

A considerable sparing of normal tissue was achieved with both ART approaches, with ReOpt being the superior technique. Compared to non-adaptive RT, the volume receiving more than 57 Gy (corresponding to 95% of the prescribed dose) was reduced to 66% (range 48–100%) for PlanSelect and to 41% (range 33–50%) for ReOpt.

Conclusion

This study demonstrated a considerable normal tissue sparing potential of ART for bladder irradiation, with clearly superior results by daily adaptive re-optimisation.     

Institut Curie guidelines on breast target volume delineation for patients treated in lateral position

PurposeTo develop guidelines for and describe the delineation of breast for patients treated in lateral position and to transform this three-dimensional technique based on the virtual simulation to volume-based modern intensity-modulated irradiation technique.Material and methodsIn our department, during the daily delineation, radiation oncologists specialized in breast cancer treatment sought consensus on the delineation of clinical treatment volume of the breast through dialogue based on cases. A radiation oncologist delineated clinical treatment volumes on CT scans of five to 20 patients, followed by a discussion and adaptation of the delineation between all radiation oncologists of the team. The consensus established between clinicians was discussed, corrected and improved. All patients were delineated in treatment position; skin markers were used to visualize the breast tissue after careful palpation.ResultsBreast clinical treatment volume was situated and delineated between pectoral muscle and 5 mm below the skin (dosimetric considerations), within the space outlined by skin markers, that showed the limits of the palpable breast tissue. In lateral position some vessels were very useful to define the limits as rami mammarii (from thoracica interna) for the internal one and thoracica lateralis for the external. This is the first atlas proposed for the delineation of the breast clinical treatment volumes for breast cancer using alternative technique of breast irradiation (lateral).ConclusionThis atlas will be helpful for the volume definition in our daily practice of breast irradiation in lateral position and can open perspectives to develop also atlases for other alternative techniques as treatment in prone position.     

Outcomes and Profiles of Older Patients Receiving Definitive Radiation Therapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center

PurposeOur purpose was to evaluate the outcomes and profiles of older patients with muscle-invasive bladder cancer (MIBC) treated with definitive radiation therapy (RT) with or without chemotherapy (CHT) at a tertiary medical center.Methods and MaterialsA retrospective study was conducted for older patients with MIBC who were ≥70 years old and underwent RT with or without CHT between 2000 and 2016. Overall survival (OS) was estimated using the Kaplan-Meier method. Disease-specific survival (DSS), cumulative incidence of progression, patterns of recurrence, and toxicities were examined. Univariate analyses were performed to identify variables associated with OS, DSS, and cumulative incidence of progression, using the Cox proportional hazards model.ResultsA total of 84 patients underwent definitive RT with or without CHT. Of these, only 29% were deemed medically fit to undergo radical cystectomy, and the remainder were medically unfit or had surgically unresectable disease. Median age was 81 years. Sixty-one percent, 29%, and 11% had clinical stage II, III, and IV disease, respectively. Eighty-six percent had maximal transurethral resection of bladder tumor before RT. Seventy-three percent received CHT with RT, and 27% had RT alone. Median follow-up was 5.7 years. Median OS was 1.9 years. OS was 42% and 25%, and DSS was 64% and 54% at 3 and 5 years, respectively. On univariate analysis, medical fitness to undergo radical cystectomy, receipt of CHT, lower T stage, and maximal transurethral resection of bladder tumor were associated with better OS; lower T stage was associated with better DSS. The cumulative incidence of progression was 44% and 49% at 3 and 5 years, respectively. Late grade 3 genitourinary and gastrointestinal toxicity were 15% and 4%, respectively. None had grade 4 or 5 toxicity.ConclusionsOlder patients with MIBC referred for RT were often medically unfit or had a surgically unresectable tumor. In these medically compromised patients, definitive RT with or without CHT was well tolerated and yielded encouraging treatment outcomes.     

Does the planning dose-volume histogram represent treatment doses in image-guided prostate radiation therapy? Assessment with cone-beam computerised tomography scans

Purpose

To assess the accuracy of the initial CT plan dose-volume histograms (DVH’s) for prostate, rectum and bladder by comparison to delivered doses determined from cone beam CT (CBCT) scans acquired during image-guided treatment.

Materials and methods

Twelve prostate patients were treated using daily implanted fiducial guidance and following local protocol for bladder and rectal preparation. CBCT scans were acquired twice weekly and contoured for prostate, rectum and bladder. The planned beams were applied to all CBCT scans to determine the delivered doses. Prostate dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 40 Gy, 60 Gy and 70 Gy at treatment were compared to the initial plan, with significance determined using the one-sample t-test.

Results

Four patients showed marginally compromised CTV coverage by the 95% isodose at all CBCT plans. For nine patients the initial plan rectal DVH was significantly outside the range of the treatment DVH’s.

Conclusions

Dose coverage of the prostate was not achieved for all patients. Observed rectal and bladder doses were higher than predicted. The initial treatment plan cannot be assumed to represent accurate normal tissue doses.     

Radiotherapy in muscle-invasive bladder cancer: the latest research progress and clinical application

The role of radiotherapy (RT) in the management of urinary bladder cancer has undergone several alterations along the last decades. Recently, many protocols have been developed supporting the use of multi-modality therapy, and the concept of organ preservation began to be reconsidered. Advances in radiotherapy planning, verification, and delivery provide a method to optimize radiotherapy for bladder cancer and overcome difficulties which have previously limited the success of this treatment. They offer the opportunity to enhance the therapeutic ratio by reducing the volume of normal tissue irradiated and by increasing radiation dose or using more intensive fractionation and synchronous chemotherapy regimes. These techniques have a large potential to improve the therapeutic outcome of bladder cancer. In the near future, it should be possible to offer selected patients with muscle-invasive bladder cancer an organ-sparing, yet effective combined-modality treatment. In this review, we aim to present the role of radiotherapy in the management of muscle invasive bladder cancer. Alternative methods of improving treatment accuracy such as helical tomotherapy, adaptive radiotherapy and radiochemotherapy are also discussed.