The aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [177Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. Methods: Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [177Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. Results: A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (P = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. Conclusion: Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials.

e16291 Background: The QoL experience during the 1st year of follow up for 68Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index < 30%, adequate organ function & ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68Ga-DOTATATE PET were eligible to proceed to 177Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 & 12 (±2) mths were available in 174,128 & 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the “lung” compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ≥1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (σ2 hCT-AC = 5.5%/4.7%/2.7% vs σ2 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.

630 Background: 177Lu DOTATATE therapy can potentially improve progression free survival (PFS) and overall survival (OS) in patients (pts) with progressive metastatic neuroendocrine tumors. Individualized dosimetry can be used to tailor treatment doses. A multi-institutional prospective single arm study of 177Lu DOTATATE (planned 4 cycles), with individualized dosimetry, in pts with 68Ga DOTATATE positive, progressive metastatic disease is ongoing by the Cancer Care Ontario Neuroendocrine Tumor (CCO NET) consortium in Ontario (NCT02743741). 68Ga DOTATATE PET scans are performed prior to therapy to confirm positive disease. Dosimetry calculations are based on SPECT/CT images acquired at 4, 24 and 72 hours following 177Lu DOTATATE therapy. A 2cm sphere is placed over normal renal cortex in both kidneys, and over a reference vertebral body to estimate renal and bone marrow (BM) dose. All pts receive a standard 200mCi for cycle 1 of therapy (with modifications based on creatinine clearance and hematology for all cycles). Residual renal tolerance absorbed dose after cycle 1 is evenly divided across the remaining cycles and an injected activity recommended. This process is repeated after each successive cycle. We applied the same methodology to estimate absorbed dose delivered to hepatic tumors and normal liver. The liver is segmented to provide a bounding box to estimate dose. We use 41%Max of the uptake within the entire liver as the cut-off to represent regions of tumor involvement. Results: One hundred subjects were accrued from August 2016 - December 2018 from the four consortium sites. To date, 282 cycles of 177LuDOTATATE have been delivered, and 94 baseline 68Ga PET scans have been performed. The PET positive rate was 96% (90/94) (including one equivocal case). Of these, 62 patients have completed their therapeutic phase and 53 (85%) have completed all 4 cycles of therapy. Five pts have died due to progressive disease during treatment, three had treatment discontinued early due to progressive disease and one had treatment discontinued due to comorbidities. Of the 53 patients who have completed all four cycles, the median injected activity was 983 (SD 193, range 357-1158) mCi, with 9 pts receiving the standard dose (800 mCi±10%), 8 pts dose reduced (720 mCi), and 36 pts (68%) receiving an escalated dose (880 mCi). For all pts the cumulative renal absorbed dose received was 23Gy except one (total 177Lu DOTATATE dose 865mCi). All pts received <2Gy BM exposure except 4 pts. High BM dose was typically due to diffuse bone metastases. The median proportion of liver >41%Max was 3 (SD 8) %. The median dose to the regions >41%Max was 18 (SD14) Gy per cycle. In contrast, the dose delivered to region of the liver that is 41% Max was 2.4 (SD2.5) Gy per cycle. Conclusions: Individualized dosimetry allowed dose escalation in 68% of pts while maintaining renal exposure within tolerance. The dose delivered to the tumor containing regions is estimated to be approximately 84Gy over 4 cycles. Longer term follow-up is required to determine whether outcomes are enhanced due to the incorporation of individualized dosimetry.

PURPOSE:To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer.MATERIALS AND METHODS:Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions.RESULTS:Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients).CONCLUSION:The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. These are reviewed with an effort to highlight challenges related to quantification and reproducibility. In addition, several of the emerging applications of these imaging approaches are also highlighted. Finally, the growing community of support for establishing quantitative imaging approaches as we move toward clinical evaluation is summarized and the need for a clinical service in support of the clinical science and delivery of care is proposed. Semin Radiat Oncol 25:292-304 (C) 2015 Published by Elsevier Inc.

Purpose: Although isolated intra-prostatic recurrence after radiotherapy may be curable with local salvage, toxicity remains of concern. Targeting the recurrent tumor volume for salvage brachytherapy may result in reduced morbidity without compromising efficacy provided it is sufficiently accurate. We evaluated the performance of MRI (plus/minus biopsy) in detecting and delineating GTV boundaries.Materials and Methods: Patients with biochemical failure after radiotherapy were enrolled in a prospective clinical trial in order to map sites of local recurrence. An integrated diagnostic MRI and interventional mapping biopsy procedure was performed under sedation in a 1.5T scanner. Patients were imaged with a pelvic coil and an endorectal coil attached to a stereotactic transperineal template assembly. Diagnostic fast spin echo (FSE) T2-weighted (T2w), diffusion weighted (DWI), and dynamic contrast enhanced (DCE) images were acquired, followed by targeted biopsy of suspicious regions and random sextant sampling of the normal-appearing peripheral zone. Diagnostic images were reviewed off-line by 2 blinded expert observers who delineated suspicious regions to generate gross target volumes (GTVs) for brachytherapy. Image voids corresponding to biopsy cores locations were delineated and registered onto diagnostic T2w images using point-based rigid image registration to account for prostate displacement during needle insertion. The delineation accuracy of MRI alone, and MRI + 5mm expansion margin was determined against overlaid histology maps. Adequacy of GTV coverage was assessed by whether all pathological proven tumour sites were within delineated boundaries.Results: Of the 18 patients enrolled and analysed to date, the majority (83%) were found to have local recurrence. Patients with less than 6 informative cores were excluded, leaving 12 (Observer 1) and 15 patients (Observer 2) available for analysis. Observers performed comparably, whereby mean MRI sensitivity, specificity, PPV and NPV for detecting tumor was 0.76, 0.7, 0.7, and 0.75. The MRI GTV boundary was consistent with histology in 5/15 patients, and improved to 8/15 patients with addition of a 5mm expansion margin. Targeted biopsies improved the accuracy of GTV delineation to 14/15 patients, by excluding false positive GTVs (2 patients), increasing target volumes (2 patients) or both (2 patients). Random sampling biopsy was only relevant in 1 patient by detecting tumour not identified by MRI and targeted biopsy.Conclusions: MRI is a promising tool to detect intra-prostatic regions of tumor recurrence, but is not sufficiently accurate to define boundaries for tumor-targeted salvage brachytherapy even with addition of an uncertainty margin. Targeted biopsy improved both the detection and delineation accuracy of GTVs, and changed brachytherapy planning in 40% of patients. Purpose: Although isolated intra-prostatic recurrence after radiotherapy may be curable with local salvage, toxicity remains of concern. Targeting the recurrent tumor volume for salvage brachytherapy may result in reduced morbidity without compromising efficacy provided it is sufficiently accurate. We evaluated the performance of MRI (plus/minus biopsy) in detecting and delineating GTV boundaries. Materials and Methods: Patients with biochemical failure after radiotherapy were enrolled in a prospective clinical trial in order to map sites of local recurrence. An integrated diagnostic MRI and interventional mapping biopsy procedure was performed under sedation in a 1.5T scanner. Patients were imaged with a pelvic coil and an endorectal coil attached to a stereotactic transperineal template assembly. Diagnostic fast spin echo (FSE) T2-weighted (T2w), diffusion weighted (DWI), and dynamic contrast enhanced (DCE) images were acquired, followed by targeted biopsy of suspicious regions and random sextant sampling of the normal-appearing peripheral zone. Diagnostic images were reviewed off-line by 2 blinded expert observers who delineated suspicious regions to generate gross target volumes (GTVs) for brachytherapy. Image voids corresponding to biopsy cores locations were delineated and registered onto diagnostic T2w images using point-based rigid image registration to account for prostate displacement during needle insertion. The delineation accuracy of MRI alone, and MRI + 5mm expansion margin was determined against overlaid histology maps. Adequacy of GTV coverage was assessed by whether all pathological proven tumour sites were within delineated boundaries. Results: Of the 18 patients enrolled and analysed to date, the majority (83%) were found to have local recurrence. Patients with less than 6 informative cores were excluded, leaving 12 (Observer 1) and 15 patients (Observer 2) available for analysis. Observers performed comparably, whereby mean MRI sensitivity, specificity, PPV and NPV for detecting tumor was 0.76, 0.7, 0.7, and 0.75. The MRI GTV boundary was consistent with histology in 5/15 patients, and improved to 8/15 patients with addition of a 5mm expansion margin. Targeted biopsies improved the accuracy of GTV delineation to 14/15 patients, by excluding false positive GTVs (2 patients), increasing target volumes (2 patients) or both (2 patients). Random sampling biopsy was only relevant in 1 patient by detecting tumour not identified by MRI and targeted biopsy. Conclusions: MRI is a promising tool to detect intra-prostatic regions of tumor recurrence, but is not sufficiently accurate to define boundaries for tumor-targeted salvage brachytherapy even with addition of an uncertainty margin. Targeted biopsy improved both the detection and delineation accuracy of GTVs, and changed brachytherapy planning in 40% of patients.

Purpose: To investigate cumulative doses of soft tissue anatomy from ultrasound (US) guided HDR interstitial brachytherapy boost and external beam pelvic IMRT using deformable registration.Materials and Methods: 10 patients previously treated with EB-IMRT and IG-BT boost were retrospectively evaluated for deformation and dose accumulation.Patients were treated with whole-pelvis EBRT (46.0 Gy in 2 Gy fractions) and an ultrasound-guided HDR implant with real-time dosimetry (21.0 Gy in10.5 Gy fractions).3 gold visicoil markers (4 cm in length) are placed at the same time as the HDR catheters and are used as a localization tool for both HDR fractions and IMRT delivery.A post-implant CT without the US probe and with catheters in place was alsoobtained as a verification scan for these patients.For soft tissue anatomy, a finite element based image registration method was applied to obtain the deformation of each voxel of the region of interest on the US image.Because of US probe in the rectum and a limited field of view, US image is limited in deforming only the prostate.Post-implant CT was therefore used to deform all the soft-tissue anatomy such as bladder, rectal wall and urethra.The deformation vector field generated after deforming postimplant CT contours was used to deform the BT dose grid on to the EB CT grid and the cumulative dose was calculated.A linear-quadratic model was applied to calculate the total equivalent dose in 2Gy fractions (EQD2) with a/b51.5 for prostate and 3 for prostatic urethra, bladder and rectal wall.Cumulative EQD2 to 99 %, 95 % and 50% volume were determined for prostate.Cumulative dose-volume parameters such as V80, V100, V125 and V150 were evaluated for urethra, bladder and rectal wall.Results: EQD2 for HDR fractionation with an a/b51.5 and 3 was 72 Gy and 56.7 Gy, respectively.The mean prostate volume for EB and BT fractions were 55.4 AE 13.2 cc and 45.7 AE 9.6 cc.The mean difference between EB and BT prostate volume was 6.0 AE 10.3 cc.The average cumulative EQD2 to 99 %, 95 % and 50% of prostate volume based on rigid and deformable registration was 84.0 AE 12.9, 94.1 AE 15.6, 131.1 AE 7 Gy and 116.6 AE 12.6, 123.1 AE 7.5, 141.9 AE 6.0 Gy, respectively.The mean V80, V100, V125 and V150 based on cumulative doses for urethra were 98.6 AE 3.1, 92.9 AE 6.9, 3.2 AE 7.7, 1.2 AE 3.0 %.Conclusions: Large deformations exist in soft tissue anatomy between BT and EB fractions that have a significant impact on cumulative dose distribution.Mean variations of up to 28 % were seen for cumulative doses in prostate based on rigid and deformable registration.Ongoing work will evaluate the effect of delivered brachytherapy dose in adaptive planning optimization of external beam IMRT planning.

Purpose: Patient specific needle deflection, during transperineal needle insertion, often leads to unnecessary added trauma due to the need for repeated corrections. In the absence of real-time imaging during MRI-guided procedures, deflections may also translate to longer procedure times. This study aims to test the performance of a navigation strategy whereby deflection of the first and second needle is used to re-calibrate the stereotactic transperineal grid projection, with the goal of improving subsequent needle targeting accuracy. Materials and Methods: Patients were enrolled on a prospective clinical trial of MRI-guided transperineal mapping prostate biopsy to guide subsequent tumor-targeted HDR brachytherapy. A customized system (Aegis with Prostate) was utilized to permit transperineal needle insertion under MRI-guidance. A stereotactic transperineal grid is rigidly affixed perpendicularly to an endorectal imaging coil (ERC), and registered to images using manually defined reference landmarks filled with water-based lubricant. As in standard TRUS-guided techniques, grid coordinates are chosen to achieve target prostate locations during needle insertion. After needle insertion, an axial T2 weighted fast spin echo (FSE) verification image was acquired to determine the actual location of the needle in x and y planes. Corrections were based on the error identified with the first inserted needle as well as the mean error of the first 2 needles inserted in opposite sides of the gland. A correction based on the mean error for the entire cohort was also explored. Results: Targeting accuracy data from 19 patient procedures was analyzed, with a mean of 11 biopsies per patient (range= 6–14 biopsies). The mean in-plane vector error for all 207 biopsies was 2.8mm (SD =1.6mm). The mean lateral displacement (x) was 0.3mm (SD=2.3mm), and mean AP displacement (y) was biased posteriorly at 1.7mm (SD=1.6). Correction based on the first needle improved AP mean accuracy (0.1, SD 1.7), but reduced lateral accuracy (mean -0.6, SD 2.2). Using the mean error of the first 2 needles inserted in opposing lateral lobes of the prostate marginally improved the in-plane vector error to 2.3mm (SD 1.9mm), but eliminated bias (mean(x/y)= -0.10/-0.04, SD(x/y)= 2.33/1.61). Systematic correction utilizing the global measured mean in-plane error also showed promise in increased targeting accuracy by improving the deflection error in 16/19 patients. Conclusions: Correcting for the average targeting error of the first 2 inserted needles reduces patient-specific deflection bias in transperineal procedures as does a systematic correction based on the global measured mean in-plane error. Prospective evaluation of these navigation strategies are currently underway.

Purpose: With any elapsed time between imaging for prostate HDR brachytherapy planning and delivery, concern remains regarding the risk of patient motion and catheter retraction relative to planning conditions. Manipulation of catheters during transfer-tube connection may also cause superior-inferior (SI) displacement at the level of the prostate gland in a manner not appreciated by inspecting the template surface. Finally, the accuracy of determining the SI coordinate of the first dwell position is currently limited by the slice thickness resolution in 2.5D CT or MRI, and may be improved with the addition of high-resolution sagittal x-ray projections. We explored the use of lateral x-ray imaging during afterloader cable checks to the first dwell position for each sequential catheter. Materials and Methods: A patient enrolled on a prospective clinical trial of MRI-guided and tumor-targeted salvage HDR prostate brachytherapy constituted the study subject. Prior to catheter insertion (240mm Pro-Guide sharp needles, Nucletron), a 1x3mm gold fiducial marker (FM) (Best Medical) was implanted at the base of the prostate. The balloon of an indwelling Foley catheter (FB) was inflated with 10cc of 135mgI/mL contrast (Visipaque). The final catheter geometry was locked at the level of the MRI-compatible template (Sentinelle Medical Inc.), and metal obturators were removed during MR imaging (Axial T2-weighted FSE, 2mm slice thickness). The obturators were re-inserted prior to patient transport from the MRI to the brachytherapy suite, where they were removed before connecting to the afterloader (microSelectron V3, Nucletron). A mobile C-arm fluoroscopy unit (Siemens) acquired lateral x-rays (7Mas, 110KV) while the dummy cable was paused for 3 seconds at the first dwell position for each sequential catheter. The SI location of the first dwell position was measured relative to the FM and FB (MIPAV), and compared to the geometry derived in the MRI-based treatment plan. Results: Patient transfer was uneventful under propofal sedation with no appreciable motion and/or retraction of the catheters relative to the template surface. The time elapsed between MRI and the cable check procedure prior to brachytherapy delivery was 87 minutes. The mean SI error between actual and planned conditions was 1.4mm (SD 1.4 mm) for the FM reference, and 2.2mm (1.4mm) for the FB, reflecting a systematic 0.8mm error between these two reference positions on MRI. Catheter retraction exceeded MRI voxel resolution (2mm) in 3/18 catheters, up to 5mm. Conclusions: Despite controlled conditions and a short elapsed time, catheter retraction errors were identified. The augmentation of MRI-based planning with online x-ray imaging is now poised to improve SI accuracy through: 1) increased image resolution of the first dwell position to sub-millimeter scale, 2) correction of the treatment plan based on the actual depth of the first dwell position immediately prior to delivery, and 3) online image-guidance during brachytherapy delivery.

Purpose: To investigate cumulative doses of soft tissue anatomy from ultrasound (US) guided HDR interstitial brachytherapy boost and external beam pelvic IMRT using deformable registration.Materials and Methods: 10 patients previously treated with EB-IMRT and IG-BT boost were retrospectively evaluated for deformation and dose accumulation.Patients were treated with whole-pelvis EBRT (46.0 Gy in 2 Gy fractions) and an ultrasound-guided HDR implant with real-time dosimetry (21.0 Gy in10.5 Gy fractions).3 gold visicoil markers (4 cm in length) are placed at the same time as the HDR catheters and are used as a localization tool for both HDR fractions and IMRT delivery.A post-implant CT without the US probe and with catheters in place was alsoobtained as a verification scan for these patients.For soft tissue anatomy, a finite element based image registration method was applied to obtain the deformation of each voxel of the region of interest on the US image.Because of US probe in the rectum and a limited field of view, US image is limited in deforming only the prostate.Post-implant CT was therefore used to deform all the soft-tissue anatomy such as bladder, rectal wall and urethra.The deformation vector field generated after deforming postimplant CT contours was used to deform the BT dose grid on to the EB CT grid and the cumulative dose was calculated.A linear-quadratic model was applied to calculate the total equivalent dose in 2Gy fractions (EQD2) with a/b51.5 for prostate and 3 for prostatic urethra, bladder and rectal wall.Cumulative EQD2 to 99 %, 95 % and 50% volume were determined for prostate.Cumulative dose-volume parameters such as V80, V100, V125 and V150 were evaluated for urethra, bladder and rectal wall.Results: EQD2 for HDR fractionation with an a/b51.5 and 3 was 72 Gy and 56.7 Gy, respectively.The mean prostate volume for EB and BT fractions were 55.4 AE 13.2 cc and 45.7 AE 9.6 cc.The mean difference between EB and BT prostate volume was 6.0 AE 10.3 cc.The average cumulative EQD2 to 99 %, 95 % and 50% of prostate volume based on rigid and deformable registration was 84.0 AE 12.9, 94.1 AE 15.6, 131.1 AE 7 Gy and 116.6 AE 12.6, 123.1 AE 7.5, 141.9 AE 6.0 Gy, respectively.The mean V80, V100, V125 and V150 based on cumulative doses for urethra were 98.6 AE 3.1, 92.9 AE 6.9, 3.2 AE 7.7, 1.2 AE 3.0 %.Conclusions: Large deformations exist in soft tissue anatomy between BT and EB fractions that have a significant impact on cumulative dose distribution.Mean variations of up to 28 % were seen for cumulative doses in prostate based on rigid and deformable registration.Ongoing work will evaluate the effect of delivered brachytherapy dose in adaptive planning optimization of external beam IMRT planning.

This work recommends a new and simple-to-perform method for measuring the beam energy of an accelerator. The proposed method requires the irradiation of two monitor foils interspaced by an energy degrader. The primary advantage of the proposed method, which makes this method unique from previous energy evaluation strategies that employ the use of monitor foils, is that this method is independent of the detector efficiency calibration. This method was evaluated by performing proton activation of natCu foils using both a cyclotron and a tandem Van de Graaff accelerator. The monitor foil activities were read using a dose calibrator set to an arbitrary calibration setting. Excellent agreement was noted between the nominal and measured proton energies.

Purpose: Despite a strong rationale and enthusiasm for distinguishing regions of tumor-dense burden within the prostate gland for specific dose delivery, methods and tools for clinical investigation have not yet matured. A technique is presented for integrating pathologically referenced multiparametric MRI using deformable registration for HDR brachytherapy planning. Materials and Methods: Four patients enrolled on a prospective trial of tumor-targeted MRI-guided HDR salvage brachytherapy were evaluated, each receiving two fractions over 10 days. Multiparametric online MRI-guided prostate biopsy with 3D image verification of needle core locations enabled cores and suspicious tumor volumes to be mapped onto T2 MRI. The GTV was defined as the shared boundary of suspicious image features and malignant biopsy cores. On treatment day, radiation oncologist estimated the intended GTV boundary based on common anatomical MRI landmarks. Inverse treatment planning utilized IPSA objectives to achieve tumor V11Gy>95% and prostate V8Gy>95%, while respecting OAR constraints. MORFEUS, a biomechanical model-based deformable image registration technique, was used to perform deformable registration of diagnostic images acquired during biopsy onto the brachytherapy planning image. Common 3D points in the prostate were identified to determine the absolute error between the observed and MORFEUS-predicted point displacements. The registered GTV was compared with the estimated GTV using Dice's coefficient and tumor D98 and V11Gy. Results: The average absolute error of point displacement was 0.5mm LR, 1.3mm AP and 1.3mm SI. The average Dice's coefficient was 0.75. The majority of the geometric discrepancy occurred in the SI dimension (Figure 1, registered and estimated GTV in blue and orange, respectively). The registered GTV received higher than intended dose in 5/7 fractions (D98 range 10.0Gy - 13.1Gy). Tumor coverage was compromised in 2/7 fractions with the estimated technique (V11Gy range 85.6% - 100%). Conclusions: Feasibility of integrating pathologically referenced multiparametric MRI for GTV delineation during HDR prostate brachytherapy has been demonstrated. The accuracy achieved with the deformable registration was smaller than the largest voxel dimension. A small, but potentially relevant dosimetric discrepancy between estimated and deformably registered GTV was observed. Ongoing work will explore strategies to improve AP registration accuracy, and streamline procedures to enable online use.

The objective of this work is to assess the suitability and performance of a new dosimeter system with a novel geometry for the quality assurance (QA) of volumetric modulated arc therapy (VMAT). The new dosimeter system consists of a hollow cylinder (15 and 25 cm inner and outer diameters) with 124 diodes embedded in the phantom's cylindrical wall forming four rings of detectors. For coplanar beams, the cylindrical geometry and the ring diode pattern offer the advantage of invariant perpendicular incidence on the beam central axis for any gantry angle and also have the benefit of increasing the detector density as both walls of the cylinder sample the beam. Other advantages include real-time readout and reduced weight with the hollow phantom shape. A calibration method taking into account the variation in radiation sensitivity of the diodes as a function of gantry angle was developed and implemented. In this work, the new dosimeter system was used in integrating mode to perform composite dose measurements along the cylindrical surface supporting the diodes. The reproducibility of the dosimeter response and the angular dependence of the diodes were assessed using simple 6 MV photon static beams. The performance of the new dosimeter system for VMAT QA was then evaluated using VMAT plans designed for a head and neck, an abdominal sarcoma, and a prostate patient. These plans were optimized with 90 control points (CPs) and additional versions of each plan were generated by increasing the number of CPs to 180 and 360 using linear interpolation. The relative dose measured with the dosimeter system for the VMAT plans was compared to the corresponding TPS dose map in terms of relative dose difference (% deltaD) and distance to agreement (DTA). The dosimeter system's sensitivity to gantry rotation offset and scaling errors as well as setup errors was also evaluated. For static beams, the dosimeter system offered good reproducibility and demonstrated small residual diode angular dependence after calibration. For VMAT deliveries, the agreement between measured and calculated doses was good with > or = 86.4% of the diodes satisfying 3% of % deltaD or 2 mm DTA for the 180 CP plans. The phantom offered sufficient sensitivity for the detection of small gantry rotation offset (3 degrees) and scaling errors (1 degree) as well as phantom setup errors of 1 mm, although the results were plan dependent. With its novel geometry, the dosimeter system was also able to experimentally demonstrate the discretization effect of the number of CPs used in the TPS to simulate a continuous arc. These results demonstrate the suitability of the new dosimeter system for the patient-specific QA of VMAT plans and suggest that the dosimeter system can be an effective tool in the routine QA and commissioning of treatment machines capable of VMAT delivery and cone-beam CT image guidance.