D. Pradhan

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patients skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patients tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was approximately 4.0 cGy, which was approximately 40% higher than the Rt Lat dose of approximately 2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm x 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patients Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370 degrees scan rotation (10 degrees scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of approximately 10-11 cGy while the right hip received approximately 6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than approximately 12% to the table-drop setup.

Evaluation of multiple image-based modalities for image-guided radiation therapy (IGRT) of prostate carcinoma: A prospective study

PURPOSE Setup errors and prostate intrafraction motion are main sources of localization uncertainty in prostate cancer radiation therapy. This study evaluates four different imaging modalities 3D ultrasound (US), kV planar images, cone-beam computed tomography (CBCT), and implanted electromagnetic transponders (Calypso/Varian) to assess inter- and intrafraction localization errors during intensity-modulated radiation therapy based treatment of prostate cancer. METHODS Twenty-seven prostate cancer patients were enrolled in a prospective IRB-approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall, 1100 fractions were evaluated. For each fraction, treatment targets were localized using US, kV planar images, and CBCT in a sequence defined to determine setup offsets relative to the patient skin tattoos, intermodality differences, and residual errors for each patient and patient cohort. Planning margins, following van Herks formalism, were estimated based on error distributions. Calypso-based localization was not available for the first eight patients, therefore centroid positions of implanted gold-seed markers imaged prior to and immediately following treatment were used as a motion surrogate during treatment. For the remaining 19 patients, Calypso transponders were used to assess prostate intrafraction motion. RESULTS The means (μ), and standard deviations (SD) of the systematic (Σ) and random errors (σ) of interfraction prostate shifts (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and US, averaged over all patients and fractions, were: [μ CBCT = (-1.2, 0.2, 1.1) mm, Σ CBCT = (3.0, 1.4, 2.4) mm, σ CBCT = (3.2, 2.2, 2.5) mm], [μkV = (-2.9, -0.4, 0.5) mm, Σ kV = (3.4, 3.1, 2.6) mm, σ kV = (2.9, 2.0, 2.4) mm], and [μ US = (-3.6, -1.4, 0.0) mm, Σ US = (3.3, 3.5, 2.8) mm, σ US = (4.1, 3.8, 3.6) mm], in the anterior-posterior (A/P), superior-inferior (S/I), and the left-right (L/R) directions, respectively. In the treatment protocol, adjustment of couch was guided by US images. Residual setup errors as assessed by kV images were found to be: μ residual = (-0.4, 0.2, 0.2) mm, Σ residual = (1.0, 1.0,0.7) mm, and σ residual = (2.5, 2.3, 1.8) mm. Intrafraction prostate motion, evaluated using electromagnetic transponders, was: μ intrafxn = (0.0, 0.0, 0.0) mm, Σ intrafxn = (1.3, 1.5, 0.6) mm, and σ intrafxn = (2.6, 2.4, 1.4) mm. Shifts between pre- and post-treatment kV images were: μ kV(post-pre) = (-0.3, 0.8, -0.2), Σ kV(post-pre) = (2.4, 2.7, 2.1) mm, and σ kV(post-pre) = (2.7, 3.2, 3.1) mm. Relative to skin tattoos, planning margins for setup error were within 10-11 mm for all image-based modalities. The use of image guidance was shown to reduce these margins to less than 5 mm. Margins to compensate for both residual setup (interfraction) errors as well as intrafraction motion were 6.6, 6.8, and 3.9 mm in the A/P, S/I, and L/R directions, respectively. CONCLUSIONS Analysis of interfraction setup errors, performed with US, CBCT, planar kV images, and electromagnetic transponders, from a large dataset revealed intermodality shifts were comparable (within 3-4 mm). Interfraction planning margins, relative to setup based on skin marks, were generally within the 10 mm prostate-to-planning target volume margin used in our clinic. With image guidance, interfraction residual planning margins were reduced to approximately less than 4 mm. These findings are potentially important for dose escalation studies using smaller margins to better protect normal tissues.

Examining Margin Reduction and Its Impact on Dose Distribution for Prostate Cancer Patients Undergoing Daily Cone-Beam Computed Tomography

PURPOSE To examine the dosimetric impact of margin reduction and quantify residual error after three-dimensional (3D) image registration using daily cone-beam computed tomography (CBCT) for prostate cancer patients. METHODS AND MATERIALS One hundred forty CBCTs from 5 prostate cancer patients were examined. Two intensity-modulated radiotherapy plans were generated on CT simulation on the basis of two planning target volume (PTV) margins: 10 mm all around the prostate and seminal vesicles except 6 mm posteriorly (10/6) and 5 mm all around except 3 mm posteriorly (5/3). Daily CBCT using the Varian On-Board Imaging System was acquired. The 10/6 and 5/3 simulation plans were overlaid onto each CBCT, and each CBCT plan was calculated. To examine residual error, PlanCT/CBCT intensity-based 3D image registration was performed for prostate localization using center of mass and maximal border displacement. RESULTS Prostate coverage was within 2% between the 10/6 and 5/3 plans. Seminal vesicle coverage was reduced with the 5/3 plan compared with the 10/6 plan, with coverage difference within 7%. The 5/3 plan allowed 30-50% sparing of bladder and rectal high-dose regions. For residual error quantification, center of mass data show that 99%, 93%, and 96% of observations fall within 3 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. Maximal border displacement observations range from 79% to 99%, within 5 mm for all directions. CONCLUSION Cone-beam CT dosimetrically validated a 10/6 margin when soft-tissue localization is not used. Intensity-based 3D image registration has the potential to improve target localization and to provide guidelines for margin definition.

Radiation therapy for Retinoblastoma: A retrospective review of 120 patients

PURPOSE To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, Saudi Arabia from 1976 to 1993. METHODS AND MATERIALS A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the alpha/beta ratio for early effects and tumor control at 10, Tk = 21 days, Tpot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy10 for early effects, and 101 Gy3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months. RESULTS Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had positive CSF cytology, bone scan, or bone marrow examination. In Group C 19% had positive CSF cytology, and bone marrow, and 14% had a positive bone scan. CONCLUSIONS 1) EBORT preserved useful vision in a significant proportion of patients even in eyes with advanced RE Stage RB, but longer follow-up is likely to reveal an even higher complication rate with this regime. 2) High dose per fraction probably contributed to the increased complications. 3) Chemotherapy did not demonstrate any effect on retaining vision in this study. 4) For disease that is confined to within the eye clinically and radiologically, invasive procedures for CSF cytology, bone marrow examination, and bone scan do not seem warranted. 5) The optimum technique, fractionation, and dosage for RB is still not well defined.

Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

PURPOSE To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. METHODS AND MATERIALS Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. RESULTS Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. CONCLUSIONS Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.

Comparison of similarity measures for rigid-body CT/dual X-ray image registrations

A set of experiments were conducted to evaluate six similarity measures for intensity-based rigid-body 3D/2D image registration. Similarity measure is an index that measures the similarity between a digitally reconstructed radiograph (DRR) and an x-ray planar image. The registration is accomplished by maximizing the sum of the similarity measures between biplane x-ray images and the corresponding DRRs in an iterative fashion. We have evaluated the accuracy and attraction ranges of the registrations using six different similarity measures on phantom experiments for head, thorax, and pelvis. The images were acquired using Varian Medial System On-Board Imager. Our results indicated that normalized cross correlation and entropy of difference showed a wide attraction range (62 deg and 83 mm mean attraction range, ωmean), but the worst accuracy (4.2 mm maximum error, emax). The gradient-based similarity measures, gradient correlation and gradient difference, and the pattern intensity showed sub-millimeter accuracy, but narrow attraction ranges (ωmean=29 deg, 31 mm). Mutual information was in-between of these two groups (emax=2.5 mm, ωmean= 48 deg, 52 mm). On the data of 120 x-ray pairs from eight IRB approved prostate patients, the gradient difference showed the best accuracy. In the clinical applications, registrations starting with the mutual information followed by the gradient difference may provide the best accuracy and the most robustness.

Prostate Localization on Daily Cone-Beam Computed Tomography Images: Accuracy Assessment of Similarity Metrics

PURPOSE To evaluate different similarity metrics (SM) using natural calcifications and observation-based measures to determine the most accurate prostate and seminal vesicle localization on daily cone-beam CT (CBCT) images. METHODS AND MATERIALS CBCT images of 29 patients were retrospectively analyzed; 14 patients with prostate calcifications (calcification data set) and 15 patients without calcifications (no-calcification data set). Three groups of test registrations were performed. Test 1: 70 CT/CBCT pairs from calcification dataset were registered using 17 SMs (6,580 registrations) and compared using the calcification mismatch error as an endpoint. Test 2: Using the four best SMs from Test 1, 75 CT/CBCT pairs in the no-calcification data set were registered (300 registrations). Accuracy of contour overlays was ranked visually. Test 3: For the best SM from Tests 1 and 2, accuracy was estimated using 356 CT/CBCT registrations. Additionally, target expansion margins were investigated for generating registration regions of interest. RESULTS Test 1-Incremental sign correlation (ISC), gradient correlation (GC), gradient difference (GD), and normalized cross correlation (NCC) showed the smallest errors (mu +/- sigma: 1.6 +/- 0.9 approximately 2.9 +/- 2.1 mm). Test 2-Two of the three reviewers ranked GC higher. Test 3-Using GC, 96% of registrations showed <3-mm error when calcifications were filtered. Errors were left/right: 0.1 +/- 0.5mm, anterior/posterior: 0.8 +/- 1.0mm, and superior/inferior: 0.5 +/- 1.1 mm. The existence of calcifications increased the success rate to 97%. Expansion margins of 4-10 mm were equally successful. CONCLUSION Gradient-based SMs were most accurate. Estimated error was found to be <3 mm (1.1 mm SD) in 96% of the registrations. Results suggest that the contour expansion margin should be no less than 4 mm.

Contouring variability of human- and deformable-generated contours in radiotherapy for prostate cancer

This study was designed to evaluate contouring variability of human-and deformable-generated contours on planning CT (PCT) and CBCT for ten patients with low-or intermediate-risk prostate cancer. For each patient in this study, five radiation oncologists contoured the prostate, bladder, and rectum, on one PCT dataset and five CBCT datasets. Consensus contours were generated using the STAPLE method in the CERR software package. Observer contours were compared to consensus contour, and contour metrics (Dice coefficient, Hausdorff distance, Contour Distance, Center-of-Mass [COM] Deviation) were calculated. In addition, the first day CBCT was registered to subsequent CBCT fractions (CBCTn: CBCT2-CBCT5) via B-spline Deformable Image Registration (DIR). Contours were transferred from CBCT1 to CBCTn via the deformation field, and contour metrics were calculated through comparison with consensus contours generated from human contour set. The average contour metrics for prostate contours on PCT and CBCT were as follows: Dice coefficient-0.892 (PCT), 0.872 (CBCT-Human), 0.824 (CBCT-Deformed); Hausdorff distance-4.75 mm (PCT), 5.22 mm (CBCT-Human), 5.94 mm (CBCT-Deformed); Contour Distance (overall contour)-1.41 mm (PCT), 1.66 mm (CBCT-Human), 2.30 mm (CBCT-Deformed); COM Deviation-2.01 mm (PCT), 2.78 mm (CBCT-Human), 3.45 mm (CBCT-Deformed). For human contours on PCT and CBCT, the difference in average Dice coefficient between PCT and CBCT (approx. 2%) and Hausdorff distance (approx. 0.5 mm) was small compared to the variation between observers for each patient (standard deviation in Dice coefficient of 5% and Hausdorff distance of 2.0 mm). However, additional contouring variation was found for the deformable-generated contours (approximately 5.0% decrease in Dice coefficient and 0.7 mm increase in Hausdorff distance relative to human-generated contours on CBCT). Though deformable contours provide a reasonable starting point for contouring on CBCT, we conclude that contours generated with B-Spline DIR require physician review and editing if they are to be used in the clinic.

SU‐FF‐T‐60: A Simplified Frame Work Using Deep Inspiration Breath‐Hold (DIBH) for the Treatment of Left Breast Cancer with Improved Heart Sparing

Purpose: To develop a simplified frame work using deep inspiration breath‐hold (DIBH) for left breast treatment. Materials and Methods: The current version of Varians RPM system was rarely used in amplitude gating mode, especially with breath hold. The major reason is that the breathing amplitude is much less reproducible than breathing phase. Further, the same signal captured by the infrared camera in simulation room and that in treatment room could be different in amplitude. In this study, we presented a simplified frame work to improve the reproducibility of patients breathing amplitude. First, an aqua‐plastic body mask of 1.0–1.5 in wide was made right before patients simulation while the patient is in DIBH. The body mask was set at umbilicus right superior to the marker box. It will then be used to guide the patient herself for DIBH. The DIBH signal is also displayed on a computer monitor set close to patient, which is a duplicate display of the DIBH signal in the RPM computer. The patient can see her own signal and can therefore guide her breath such that relatively constant amplitude can be achieved. Results: The frame work was tested by a few volunteers and all agree that the system is feasible for left breast treatment. The DIBH can last 15–35s with good constant amplitude. In case the captured amplitude is different in treatment room, the two gating threshold lines set in simulation can be adjusted overlay to the DIBH signal before treatment. Conclusion: The system is feasible for the treatment of left breast cancer with DIBH. Further improvement can be made by wiring the gating cable through patient using two electrodes; one on patients body and the other on the guiding mask so that the amplitude‐gated CT scans and treatment can be actively controlled by patient herself.

Do Sociodemographic Factors Influence Outcome in Prostate Cancer Patients Treated With External Beam Radiation Therapy

Objectives:The purpose of this study was to analyze the prognostic significance of sociodemographic factors on biochemical control (bNED) and overall survival (OS) in patients with prostate cancer. Methods:Prostate cancer patients treated with definitive external beam radiation therapy (EBRT)±hormone therapy from 1997 to 2006 were analyzed in this IRB-approved study. Patient demographics, treatment (Tx), and clinical outcome were obtained from electronic medical records. Median household income (mHHI) at the census block group level was obtained from the 2000 census data. Data on disease and Tx parameters included Gleason score, pre-Tx prostate-specific antigen (PSA), T stage, year of Tx, EBRT dose, and use of hormone therapy. Patients were categorized as having low-risk, intermediate-risk, or high-risk disease. Sociodemographic factors included age, race, marital status, and mHHI. Biochemical failure was defined as nadir PSA+2 ng/mL. OS was based on death from any cause. Results:A total of 788 consecutive patients were studied with a median follow-up of 7 years (range, 0.4 to 15 y). African Americans comprised 48% of the patients, whereas 46% of patients were white and 6% were other races. Whites had an average mHHI of