SPECT/CT image-based dosimetry for Yttrium-90 radionuclide therapy: Application to treatment response.

This work demonstrates the efficacy of voxel-based 90 Y microsphere dosimetry utilizing post-therapy SPECT/CT imaging and applies it to the prediction of treatment response for the management of patients with hepatocellular carcinoma (HCC). A 90 Y microsphere dosimetry navigator (RapidSphere) within a commercial platform (Velocity, Varian Medical Systems) was demonstrated for three microsphere cases that were imaged using optimized bremsstrahlung SPECT/CT. For each case, the 90 Y SPECT/CT was registered to follow-up diagnostic MR/CT using deformable image registration. The voxel-based dose distribution was computed using the local deposition method with known injected activity. The system allowed the visualization of the isodose distributions on any of the registered image datasets and the calculation of dose-volume histograms (DVHs). The dosimetric analysis illustrated high local doses that are characteristic of blood-flow directed brachytherapy. In the first case, the HCC mass demonstrated a complete response to treatment indicated by a necrotic region in follow-up MR imaging. This result was dosimetrically predicted since the gross tumor volume (GTV) was well covered by the prescription isodose volume (V150 Gy = 85%). The second case illustrated a partial response to treatment which was characterized by incomplete necrosis of an HCC mass and a remaining area of solid enhancement in follow-up MR imaging. This result was predicted by dosimetric analysis because the GTV demonstrated incomplete coverage by the prescription isodose volume (V470 Gy = 18%). The third case demonstrated extrahepatic activity. The dosimetry indicated that the prescription (125 Gy) isodose region extended outside of the liver into the duodenum (178 Gy maximum dose). This was predictive of toxicity as the patient later developed a duodenal ulcer. The ability to predict outcomes and complications using deformable image registration, calculated isodose distributions, and DVHs, points to the clinical utility of patient-specific dose calculations for 90 Y radioembolization treatment planning.

PET lesion segmentation using automated iso-intensity contouring in head and neck cancer.

To improve the objectivity of the integration of positron emission tomography (PET), we used the conformality index (CI) to measure the goodness of fit of a given PET iso-SUV (standardized uptake value) level with the GTV defined on PET (GTV(PET)) and CT (GTV(CT)). Twenty-two datasets involving 20 head and neck cancer patients were identified. GTV(PET) and GTV(CT) were delineated manually.An iso-intensity method was developed to automatically segment GTV(PET-ISO) using (a) SUV and (b) maximum intensity thresholding (% Max), over a range of intensities. For each intensity, GTV(PET-ISO) was compared to GTV(PET) using the conformality index CI(PET) (and, similarly, to GTV(CT) using CICT). Comparing GTV(PET) to GTV(PET-ISO) vs comparing GTV(CT) to GTV(PET-ISO), the average peak CI was 0.68 +/- 0.09 vs 0.49 +/- 0.12 (p < 0.001), the optimum iso-SUV was 2.7 +/- 0.7 vs 2.9 +/- 1.0 (p=0. 253), and the % Max SUV was 21.8% +/- 7.6% vs 23.8% +/- 8.6% (p=0. 310), respectively. The radiation oncologist's volumes corresponded to a lower iso-SUV (3.02 +/- 0.58 vs 4.36 +/- 0.77, p< 0.001) and lower % Max SUV (24.1 +/- 9.1% vs 34.3 +/- 11.2%, p<0.001) than those drawn by the nuclear medicine physician. Though manual editing may still be necessary, PET iso-contouring is one method to improve the objectivity of GTV definition in head and neck cancer patients. Iso-SUV's can also be used to study the differences between PET's role as a nuclear medicine diagnostic test versus a radiation oncology treatment planning tool.

Automated data mining of a proprietary database system for physician quality improvement.

PURPOSE: Physician practice quality improvement is a subject of intense national debate. This report describes using a software data acquisition program to mine an existing, commonly used proprietary radiation oncology database to assess physician performance. METHODS AND MATERIALS: Between 2003 and 2004, a manual analysis was performed of electronic portal image (EPI) review records. Custom software was recently developed to mine the record-and-verify database and the review process of EPI at our institution. In late 2006, a report was developed that allowed for immediate review of physician completeness and speed of EPI review for any prescribed period. RESULTS: The software extracted >46,000 EPIs between 2003 and 2007, providing EPI review status and time to review by each physician. Between 2003 and 2007, the department EPI review improved from 77% to 97% (range, 85.4-100%), with a decrease in the mean time to review from 4.2 days to 2.4 days. The initial intervention in 2003 to 2004 was moderately successful in changing the EPI review patterns; it was not repeated because of the time required to perform it. However, the implementation in 2006 of the automated review tool yielded a profound change in practice. Using the software, the automated chart review required approximately 1.5 h for mining and extracting the data for the 4-year period. CONCLUSION: This study quantified the EPI review process as it evolved during a 4-year period at our institution and found that automation of data retrieval and review simplified and facilitated physician quality improvement.

Treatment efficiency of volumetric modulated arc therapy in comparison with intensity-modulated radiotherapy in the treatment of prostate cancer.

PURPOSE: Treatment with intensity-modulated radiation therapy (IMRT) is increasingly standard for prostate cancer. Volume-modulated arc therapy (VMAT) to deliver IMRT potentially enables shorter treatment time. The aim of this study was to test this hypothesis by measuring the average patient in-room time with VMAT versus dynamic multileaf collimator (DMLC) IMRT. METHODS: Custom institutional software (RTMetrix) was used to mine the treatment times from the record-and-verify database. The in-room time (the time between patient entry and exit) was computed for each patient using RTMetrix. Average room time was compared between VMAT patients (n = 44) and IMRT patients (n = 99). Subgroup comparisons (1-arc or 2-arc VMAT, 5-field or 7-field IMRT, and electromagnetic transponder [Calypso] or gold-marker tracking) were performed. For all comparisons, 2-tailed, 2-sample, equal variance Student's t-tests were used. RESULTS: Average room time was significantly shorter for all VMAT versus DMLC IMRT (P = .0014) procedures, along with VMAT versus 7-field DMLC IMRT (P < .001), but not VMAT versus 5-field DMLC IMRT (P = .81). Room time was longer for Calypso versus gold seed patients (P < .001), but VMAT reduced treatment time in Calypso patients (P = .01). This resulted in Calypso VMAT patients' having similar treatment times to non-Calypso DMLC IMRT patients (P = .220). CONCLUSIONS: These data show that VMAT can shorten room times and improve patient throughput over 7-field DMLC IMRT. Additionally, the data demonstrate that treatment with VMAT permits the use of advanced prostate tracking (Calypso), resulting in similar room times as with standard 7-field DMLC IMRT with conventional tracking.

Quantitative analysis of pre- and post-treatment PET-CT scans using deformable image registration methods.

BACKGROUND AND PURPOSE: To investigate the utility of quantitative PET analysis for early prediction of local control following stereotactic body radiation therapy (SBRT). MATERIAL AND METHODS: An initial test cohort of fourteen cases and a validation cohort of twenty-three cases were analyzed. All patients had metastatic or recurrent cancer and underwent PET-CTs pre- and post- SBRT to a variety of sites. Local failure was defined as biopsy proven persistent/recurrent disease or progressive disease on radiologic imaging. Using deformable registration, radiation dose was transferred to the PET-CTs. Using the prescription isodose as the volume of interest (VOI), response was assessed by generating metabolic volume histograms (MVH). MVH curves examine metabolic heterogeneity in the VOI. Exploratory analyses of the test cohort evaluated the viability of multiple iso-SUV and iso-volumetric points selected from the MVH curves to serve as novel markers of response. Standard PET response markers (maximum/mean SUV and qualitative analysis) were also assessed. RESULTS: In the initial cohort, ten of fourteen patients achieved local control at last follow-up, a median of 225 days following post-SBRT PET. Three out of four local failures had an increase in max SUV, while all patients who achieved local control had a reduction in max SUV (p=0.01). Exploratory analyses using multiple iso-SUV and iso-volumetric points did not yield any factors associated with local control (p>0.05). In the validation cohort, lower post- treatment max SUV (p=.03) and reduction in max SUV (p<0.05) were significantly associated with local control. CONCLUSIONS: Reduction in max SUV following SBRT is associated with local control.

In vivo assay of folate receptors in nonfunctional pituitary adenomas with 99mTc-folate SPECT/CT.

UNLABELLED: The objective of this study was to evaluate the in vivo assay of folate receptors in nonfunctional pituitary adenomas using preoperative (99m)Tc-folate SPECT/CT and Western blot analysis (WBA) of surgical specimens as the standard. METHODS: Fifty-six patients (29 men, 27 women; age range, 29-82 y) with clinically nonfunctional pituitary adenomas on MRI underwent preoperative imaging using 666 MBq (18 mCi) of (99m)Tc-folate. SPECT/CT images and whole-body and lateral head planar images were acquired approximately 2 h after injection. Surgical resection took place within a week. WBA on a portion of the excised specimens assessed folate receptor expression in 49 patients. Attenuation-corrected (99m)Tc-folate SPECT/CT images were assessed qualitatively and quantitatively (maximal adenoma counts to background), with WBA as a standard. RESULTS: Integrated CT was useful for uptake localization and assisted region-of-interest placement. Qualitative interpretation of planar imaging yielded a sensitivity of 81% and specificity of 72%. Qualitative SPECT/CT yielded a sensitivity of 94% and specificity of 61%. Receiver-operating-characteristic curve analysis of quantitative uptake yielded a tumor-to-background cutoff ratio of 3.5, with a sensitivity of 81% and specificity of 83%. Scalp uptake yielded consistent results (over the brain, neck, and choroid plexus) for background when SPECT/CT misalignment artifacts were avoided. Detection of pituitary uptake on anterior-posterior and lateral images was hampered by facial uptake, which varied between patients. CONCLUSION: SPECT/CT of (99m)Tc-folate is an accurate method of assaying folate receptors in vivo and may provide a quantitative marker for identifying folate receptor-positive tumors. This method may also prove beneficial in selecting patients for folate-targeted therapy of clinically nonfunctional pituitary adenomas, for which there is currently no medical therapy.

Case study of anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (anti-[F-18] FACBC) to guide prostate cancer radiotherapy target design.

PURPOSE OF THE REPORT: Anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (FACBC) is a novel radiotracer, which has shown some promise for use with positron emission tomography (PET)/computed tomography (CT) for visualizing prostate cancer. Here we describe a case of a prostate cancer patient who underwent radiation treatment and had an FACBC scan obtained as part of a pilot study. METHODS: We explored the potential impact of FACBC on treatment planning. We registered the FACBC acquisition with the PET/CT, which required a simple translation. Then, we did a deformable image registration of the PET/CT with the planning CT-this process allowed the FACBC-defined gross tumor volume (GTVFACBC) to be projected into the planning CT. An intensity-modulated radiotherapy (IMRT) plan (plan A) not including GTVFACBC (with final dose to 81.0 Gy) was generated, as was an IMRT plan including the GTVFACBC to a final dose of 86.4 Gy (plan B). Target coverage and normal tissue dose volume histogram (DVH) endpoints were tabulated. RESULTS: In this particular patient, bladder constraints could not be met on any plan due to anatomic limitations. However, the impact on the rectal DVH could be assessed, and inclusion of the GTVFACBC did permit rectal DVH constraints to be met in plan B while maintaining target coverage and inhomogeneity constraints. CONCLUSION: In our test case, it was feasible to use FACBC to guide IMRT, and highlights the role of deformable image registration of the PET/CT with the planning CT. These findings can guide future studies incorporating FACBC into treatment planning.

Pelvic shape and prostate motion: implications for target volume design and analysis of acute toxicity.

OBJECTIVES: To study the impact of pelvic shape on prostate motion and the implications for radiotherapy target design and treatment outcomes. METHODS: A total of 3741 measurements (daily shift moves in the 3 principal directions) on 29 consecutive prostate cancer patients were reviewed. All patients had 3 prostatic fiducials placed and were tracked using kilovoltage on-board imaging. Pelvic shape was categorized into android (n = 21; 2580 measurements) and gynecoid (n = 8; 1161 measurements) (defined geometrically by postoutlet to preoutlet ratio). Multivariate analyses of means/standard deviations in each principal direction were performed using major demographic, disease, anatomic, and treatment factors as covariates. Toxicity rates were compared using Fisher exact test. RESULTS: On simple t test comparisons, no mean/standard deviation reached significance, although there was a nonsignificant (0.38 vs. 0.31 cm, P = 0.083) larger mean antero-posterior (AP) movement in the gynecoid group. On multivariate analyses, gynecoid shape (P = 0.032) significantly predicted for mean AP movement, and gynecoid shape (P = 0.045) significantly predicted for standard deviation of AP movement. Pelvic AP and RL dimensions also correlated with mean and standard movement along the respective axes. There were no differences between rates of acute (GI or GU) toxicity (P = 0.456) between the android and gynecoid groups. CONCLUSIONS: Treatment strategies that do not employ daily motion tracking may require wider planning target volume margins in gynecoid patients. Tracking the prostate daily, as done in our case using fiducials/on-board imaging, can counter differences in pelvic shape to produce similar treatment outcomes.

Integration of databases for radiotherapy outcomes analyses.

The technical nature of radiotherapy requires different data collection strategies for outcomes reporting than those required for most other disciplines in clinical medicine. To correlate advances in radiotherapy technology with treatment outcomes, it is necessary to integrate a given radiotherapy outcomes-study database with the record-and-verify database and with the global hospital database. The authors review the recent development of each of these categories of databases from the vantage point of radiotherapy. Their goal was to integrate these 3 databases for outcomes analyses in radiotherapy at their institution; this process involved (1) the construction of an interface between the record-and-verify database and the outcomes-study database and (2) the use of a bioinformatics database linking the outcomes-study database and the global hospital database. This bioinformatics database was successfully queried in a manner that allowed streamlining data flow of relevance to radiotherapy outcomes studies. Future directions of the application of this integration are discussed.

Clinical implementation and efficiency of kilovoltage image-guided radiation therapy.

This paper describes measurements of clinical efficiency and time requirements associated with image-guided radiation therapy (IGRT). In June 2004, the authors' institution installed an integrated kilovoltage (kV) imaging system attached to a medical linear accelerator for radiographic target localization. Over the past year, 242 patients have been localized with the kV radiographic imaging system for a total of 2,700 fractions. Data were analyzed by reviewing the time required for each patient's IGRT session, broken into both image acquisition and image analysis time. Average IGRT procedure time was reviewed pertaining to months, treatment sessions, disease sites, and radiation therapists. Results showed that the average IGRT procedure time was reduced from 450 to 237 seconds from June 2004 to June 2005. Further analysis revealed that each therapist showed improvement in reducing the IGRT procedure time from the first month of use to the month of June 2005. The routine use of IGRT may ultimately be performed within 3 to 4 minutes, with minimal disruption to the clinical treatment process.

The electronification of the radiation oncology treatment cycle: the promises and pitfalls of a digital department.

Radiation oncology departments are becoming more complex in terms of documentation, calculation, and delivery of therapy. Automation of such processes minimizes the likelihood of human error in each, and is clearly the direction in which the discipline is heading. The patient treatment cycle should be seamlessly integrated; unfortunately this is seldom the case given the different systems involved. We describe the Emory University experience, with cautions provided based on our lessons learned.