Edward J. Holupka

Image fusion for stereotactic radiotherapy and radiosurgery treatment planning.

PURPOSE We describe an image fusion application that addresses two basic problems that previously limited the use of magnetic resonance imaging (MRI) for geometric localization in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). The first limitation is imposed by the use of a relocatable, MRI-incompatible, stereotactic frame for stereotactic radiotherapy. The second limitation is an inherent lack of geometric fidelity in current MRI scanners that invalidates the use of MRI for stereotactic localization. METHODS AND MATERIALS We recently developed and implemented a novel automated method for fusing computerized tomography (CT) and MRI volumetric image studies. The method is based on a chamfer matching algorithm, and provides a quality assurance procedure to verify the accuracy of the fused image set. The image fusion protocol removes the need for stereotactic fixation of the patient for the MRI study. RESULTS The image fusion protocol significantly improves on the spatial accuracy of the MRI study. We demonstrate the effect of distortion and the effectiveness of the fusion with a phantom study. We present two case studies, an acoustic neurinoma treated with SRS, and a pilocytic astrocytoma treated with SRT. CONCLUSION The image fusion protocol significantly improves our logistical management of treating patients with radiosurgery and makes conformal therapy practical for treating patients with SRT. The image fusion protocol demonstrates both the superior diagnostic quality and the poor geometric fidelity of MRI. MRI is a required imaging modality in stereotactic therapy. Image fusion combines the superior MRI diagnostic quality with the superior CT geometric definition, and makes the use of MRI in stereotactic therapy possible and practical.

Real time MRI-ultrasound image guided stereotactic prostate biopsy

To report a technique for target directed transperineal ultrasound guided biopsy using high resolution endorectal MRI images Ultrasound fusion. Two patients presented after external beam irradiation for prostate cancer with a rising PSA. An Endorectal MRI using a 1.5 Tesla scanner was obtained. Subsequently a Transrectal Ultrasound guided biopsy was performed. The Ultrasound probe was fixed to a stepper-stabilizer to provide a reference coordinate system for stereotaxic needle biopsy needle placement. The MRI image set was fused to the Ultrasound images in real time. Abnormal areas determined in the MR images were targeted for biopsy. Recurrent prostate carcinoma was detected pathologically in 3 of 4 stereotactic biopsies. Abnormal areas suspicious for cancer detected on T1 weighted images obtained in a strong field Endorectal MRI scan can be targeted for stereotactic biopsy using Transrectal Ultrasound. This image guide technique may be very useful in directing biopsies.

Treatment planning for stereotactic radiosurgery of intra-cranial lesions

Stereotactic radiosurgery of intra-cranial lesions is a treatment modality where a well defined target volume receives a high radiation dose in a single treatment. Our technique delivers this dose using a set of non-coplanar arcs and small circular collimators. We use a standard linear accelerator in our treatments, and the adjustable treatment parameters are: isocenter location, gantry arc rotation interval, couch angle, collimator field size, and dose. The treatment planning phase of the treatment determines these parameters such that the target volume is sufficiently irradiated, and dose to surrounding healthy tissue and critical, dose-limiting structures is minimized. The attachment of a BRW localizing frame to the patients cranium combined with CT imaging (and optionally MRI or angiography) provides the required accuracy for localizing individual structures in the treatment volume. The treatment is fundamentally 3-dimensional and requires a volumetric assessment of the treatment plan. The selection of treatment arcs relies primarily on geometric constraints and the beams eye view concept to avoid irradiating critical structures. The assessment of a treatment plan involves isodose distributions throughout the volume and integral dose-volume histograms. We present the essential concepts of our treatment planning approach, and illustrate these in three clinical cases.

Calculated prostate cancer volume: The optimal predictor of actual cancer volume and pathologic stage

OBJECTIVES A new clinical pretreatment quantity called the calculated prostate cancer volume has been defined. The correlation between the calculated parameter and the actual prostate cancer volume, and its ability to predict for pathologic Stage T3 disease in patients with clinically localized disease, is tested. METHODS Prostate cancer volume measurements were obtained using a 3-dimensional computerized morphometric reconstruction technique on 104 whole-mounted radical prostatectomy specimens. The calculated prostate cancer volume was determined based on pretreatment clinical parameters (prostate-specific antigen [PSA], biopsy Gleason score, and prostate ultrasound volume). Linear regression was used to determine the Pearson correlation coefficients (r) between the PSA, the calculated prostate cancer volume, and the measured prostate cancer volume. Logistic regression multivariable analysis evaluating the predictive value of the pretreatment PSA, biopsy Gleason score, clinical stage, and calculated prostate cancer volume in predicting pathologic Stage T3 disease in patients with clinically organ-confined disease was performed. RESULTS The calculated prostate cancer volume (r 0.71 to 0.96) was superior to PSA (r 0.12 to 0.67) in predicting the measured prostate cancer volume over a wide range (0.02 to 9.5 cm3) of cancer volumes. The calculated prostate cancer volume was the only significant predictor (P = 0.02) of pathologic Stage T3 disease in patients with clinical Stage T1 to T2 disease on multivariable analysis. CONCLUSIONS The calculated volume of prostate cancer is superior to PSA in predicting both the pathologic prostate cancer volume and pathologic Stage T3 disease in patients with clinical Stage T1 and T2 disease. Therefore, it may be useful in determining the optimal candidates for radical prostatectomy.

Ultrasound image fusion for external beam radiotherapy for prostate cancer

PURPOSE To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determine (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real-time imaging. METHODS AND MATERIALS During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique. RESULTS The transrectal ultrasound probe enabled real-time prostate imaging. The lateral field size can be reduced to 6.08 x 5.68 cm2 +/- 0.62 x 0.48 cm2 from the standard 8 x 8 cm2 field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field is 1.75 cm2 +/- 0.85 cm2. CONCLUSION The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.

Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

PURPOSE To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). METHODS AND MATERIALS TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). RESULTS A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. CONCLUSIONS In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.

A geometric algorithm for medical image correlations.

An automatic image correlation algorithm is discussed for the cranial region which is based on the geometric properties of the second moment tensor associated with a volume. The second moment tensor of two identical volumes represented in two different coordinate frames is evaluated to obtain the set of translations, rotations, and anisotropic scaling operators which relate the two coordinate frames. The theory is presented along with a discussion of quantitative error analysis to measure the usefulness of such an algorithm in the clinical setting.

An automatic seed finder for brachytherapy CT postplans based on the Hough transform.

PURPOSE The purpose of the work is to describe a new algorithm for the automatic detection of implanted radioactive seeds within the prostate. The algorithm is based on the traditional Hough transform. A method of quality assurance is described as well as a quantitative phantom study to determine the accuracy of the algorithm. METHODS AND MATERIALS An algorithm is described which is based on the Hough transform. The Hough transform is a well known transform traditionally used to automatically segment lines and other well defined geometric objects from images. The traditional Hough transform is extended to three-dimensions and applied to CT images of seed implanted prostate glands. A method based on digitally reconstructed radiographs is described to quality assure the determined three-dimensional positions of the detected seeds. Two phantom studies utilizing eight seeds and nine seeds are described. All eight seeds form a contiguous a square while the nine seed phantom describes seeds which are placed side-by-side in groups of two and three. The algorithm is applied to the CT scans of both phantoms and the seed positions determined. RESULTS The algorithm has been commercially developed and used to perform postsurgical dosimetric assessment on approximately 1000 patients. Using the described quality assurance tool it was determined that the algorithm accurately determined the seed positions in all 1000 patients. The algorithm was also applied to the eight seed phantom. The algorithm successfully found all eight seeds as well as their seed coordinates. The average radial error was determined to be 0.9 mm. For the nine seed phantom, the algorithm correctly identified all nine seeds, with an average radial error of 3 mm. CONCLUSIONS The described algorithm is a robust, accurate, automatic, three-dimensional application for CT based seed determination.

Intraoperative treatment planning for radioactive seed implant therapy for prostate cancer

We describe a procedure for intraoperative treatment planning for seed implantation. One hundred seven treatment plans have been analyzed at the Beth Israel Deaconess Medical Center and affiliated hospitals. The average time for the intraoperative procedure was 1. 74 hours. No significant difference in dose coverage to the prostate or normal tissues was evident.

Bicalutamide alone prior to brachytherapy achieves cytoreduction that is similar to luteinizing hormone-releasing hormone analogues with less patient-reported morbidity

OBJECTIVES To compare the impact of bicalutamide (B) vs. luteinizing hormone-releasing hormone analogues (LHRHa) on prostate volume, patient-reported side effects, and postimplant urinary toxicity in the setting of interstitial brachytherapy for early-stage prostate cancer. METHODS Between May 1998 and January 2004, 81 patients received androgen-deprivation therapy (ADT) for cytoreduction prior to interstitial brachytherapy alone. Fifty-six patients received LHRHa and 25 patients received B. Prostate volumes were measured prospectively prior to initiating therapy, and then intraoperatively at the time of implant by a single, blinded ultrasonographer. Patient-reported quality of life data were obtained prospectively, and postimplant urinary toxicity (catheter dependency and need for surgical intervention) was recorded during follow-up. Median follow-up was 53 (range 23-78) months. RESULTS The median percentage prostate volume reductions of 26% for B and 32% for LHRHa were not statistically different (P = 0.61). Decrements in libido (92% vs. 44%, P < 0.001) and erectile function (79% vs. 20%) were reported in more respondents treated with LHRHa than B. The incidence of recatheterization (28% vs. 24%, P = 0.34), and the need for subsequent surgical intervention (11% vs. 4%, P = 0.16) were similar for patients treated with LHRHa and B. CONCLUSIONS The degree of prostate downsizing with B is similar to that achieved with LHRHa. B was associated with fewer patient-reported sexual side effects and similar urinary morbidity. A randomized trial is needed to establish whether LHRHa or B should be the standard of care for prostate downsizing before interstitial brachytherapy.