M. Roach

Evaluation of ultrasound-based prostate localization for image-guided radiotherapy.

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment. Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed. On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively. In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.

Radiotherapy for High Grade Clinically Localized Adenocarcinoma of the Prostate

PURPOSE We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy. RESULTS Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial probability of freedom from biochemical failure at 4 years was 23%. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64% free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome. CONCLUSIONS At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.

RADIATION THERAPY FOR THE MANAGEMENT OF BIOPSY PROVED LOCAL RECURRENCE AFTER RADICAL PROSTATECTOMY

PURPOSE We determine which clinical characteristics correlate with a successful outcome following external beam radiation for the management of biopsy proved, locally recurrent prostate cancer after radical prostatectomy. MATERIALS AND METHODS The clinical records of 34 patients who were treated at our institution with external beam radiation for biopsy proved local disease recurrence after radical prostatectomy were reviewed. Mean followup was 77.9 months after radical prostatectomy and 38.3 months after radiotherapy. Preoperative, postoperative and pathological characteristics were examined for the ability to predict failure following radiotherapy. RESULTS Of the 34 patients 9 (26%) exhibited persistently low and stable serum prostate specific antigen (PSA) (less than 0.5 ng./ml.), while 7 (21%) had an undetectable serum PSA (less than 0.1 ng./ml.) during followup. These 16 patients were considered to be successfully treated by radiation and in the remaining 18 (53%) radiation was considered to have failed. The likelihood of successful treatment at 3 years after radiotherapy for all patients was 48%. Preoperative PSA, PSA at first elevation, postoperative PSA velocity and pathological stage were not significant predictors of a successful outcome following radiation treatment. Patients with a serum PSA of 4 ng./ml. or less before receiving radiotherapy and those with a prostatectomy specimen Gleason score of 7 or less were significantly more likely to be successfully treated by radiotherapy. CONCLUSIONS Radiation therapy is a viable treatment option for select patients with biopsy proved local disease recurrence following radical prostatectomy. The chance of achieving and maintaining a persistently low and stable or undetectable serum PSA is likely in those patients with a prostatectomy specimen Gleason score of 7 or less and a pre-radiation PSA of 4.0 ng./ml. or less. More effective treatment regimens are needed for those patients in whom radical prostatectomy fails.

Loss of p16 Expression Is of Prognostic Significance in Locally Advanced Prostate Cancer: An Analysis From the Radiation Therapy Oncology Group Protocol 86–10

PURPOSE The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

Mégavoltage cone-beam CT : récents développements et applications cliniques pour la radiothérapie conformationnelle avec modulation d'intensité

The Megavoltage cone-beam (MV CBCT) system consists of a new a-Si flat panel adapted for MV imaging and an integrated workflow application allowing the automatic acquisition of projection images, cone-beam CT image reconstruction, CT to CBCT image registration and couch position adjustment. This provides a 3D patient anatomy volume in the actual treatment position, relative to the treatment isocenter, moments before the dose delivery, that can be tightly aligned to the planning CT, allowing verification and correction of the patient position, detection of anatomical changes and dose calculation. In this paper, we present the main advantages and performance of this MV CBCT system and summarize the different clinical applications. Examples of the image-guided treatment process from the acquisition of the MV CBCT scan to the correction of the couch position and dose delivery will be presented for spinal and lung lesions and for head and neck, and prostate cancers.

SU‐FF‐J‐60: Effectiveness of MVCBCT for Patients with Implanted High‐Z Material

Purpose: To exploit the penetrability of high‐energy photons of Megavoltage ConeBeam CT system (MVCBCT) to obtain 3D images of the anatomy in presence of “Non‐compatible CT” objects made of high‐Z material. Methods and Material: A new MVCBCT system integrated onto a clinical Linac was used to acquire 3D images of different phantoms and patients. The grey levels of different electron density inserts (lung to dense bone) in a CT phantom were measured with and without the presence of a small Cerrobend rod (10×15mm) on a regular CT and with the MVCBCT. MVCBCT of a Rando phantom with implanted gold markers and tooth fillings as well as patients with dental implants or with gold markers implanted in prostate were also obtained. Results: The presence of the Cerrobend object in the CT phantom scanned with a regular CT creates strong artifacts around the object and disturbs the quality of the entire image, modifying the Hounsfield numbers by an average of 10%, even 15 cm away from the rod. The grey levels of the density inserts in the CT phantom remain unchanged within 3% in presence of the Cerrobend rod for MVCBCT. Similarly, gold markers appear with the typical star pattern artifact on CTimages where a well‐defined dot is seen on MVCBCT. The tooth fillings in the MVCBCT Rando phantom do not disturb the soft tissue information around the teeth. Conclusion: Compared to the kV energy range, the presence of high‐Z material has relatively little impact on image quality of MVCBCT. Therefore, MVCBCT can complement missing information for planning or patient position verification purposes when high‐Z materials such as gold markers, tooth fillings, dental implants or hip prostheses are present. Clinical examples of each of these items will be presented. Conflict of Interest: Siemens supports this Research.

TH‐C‐J‐6B‐07: Intra‐Fractional and Inter/Intra‐Field Organ Motion and a Proposal for a New Patient Set‐Up Protocol

Purpose: Current set‐up protocols for prostate patients with gold markers receiving EBRT use orthogonal portal images acquired prior to treatment to position the patient. Times between image acquisition and treatment delivery for different gantry angles range from one to seven minutes, even longer for IMRT. During this time the prostate can shift from its corrected position. Method and Materials: An a‐Si flat panel EPID was used to acquire pre‐treatment portal images for positioning purposes. The panel was also used in fluoroscopic mode, acquisition rate of 3.5 frames/second, during treatment delivery. Movies of treatment delivery, 10–70 frames/movie, were acquired. Intra‐fractional and inter‐/intra‐field (between treatment delivery/during treatment delivery) organ motion was evaluated. Results: To date 83 of 125 days of treatment data have been processed. Initial results indicate that intra‐fractional/intra‐field organ motion is rare, only 4% of days exhibit marker center‐of‐mass moves greater than 2 mm. Intra‐fractional/inter‐field motion greater than 2 mm does however occur for a significant portion of treatment days, 31% of the processed population, appearing to occur during 45–90 second intervals. Qualitative analysis indicates that a large portion of prostate shifts occur due to gas in the colon and/or rectum. Respiration does not seem to be a significant cause of prostate motion. Voluntary global patient motion appears to contribute slightly to organ motion. Conclusion: The prostate is fairly stable for time periods comparable to treatment delivery times, yet is less stable for longer times. A new setup protocol is proposed utilizing a step‐and‐shoot method of treatment. The method of patient positioning would acquire a portal image, adjust the patient based on the image and then treat that single field. This process would be repeated for each gantry angle until treatment is completely delivered, thus reducing the time between portal image acquisition and treatment delivery for a particular gantry angle.

TU‐D‐AUD B‐08: Clinical Validation of a Novel Adaptive Approach for Patients Concurrently Treated with the Prostate and Pelvic Lymph Nodes

Purposes/Objectives: One of the challenges for concurrent irradiation of the prostate and pelvic lymph nodes with IMRT is the independent movement of the prostate and the pelvic nodes. To resolve this challenge, we proposed a novel adaptive approach using multiple adaptive IMRT plans (MAP). This study is to validate dosimetric accuracy of this adaptive approach. Method and Materials: MAP Plans for a patient included five IMRT plans with one planning prostate position and the four shifted prostate positions. Prior to each treatment, daily mega‐voltage cone beam CT (MV‐CBCT) was acquired to determine the prostate position relative to the pelvic bones, and one of the five MAP plans was selected for the treatment. Seventeen daily MV‐CBCTs were available for analysis. Seventeen verification plans were retrospectively created by applying delivery beams to daily MV‐CBCTs. For each verification plan, the daily prostate contour was created by shifting the planning contour with the measured prostate movement and the daily pelvic lymph nodal volume was transferred from the planning CT to the MV‐CBCT using rigid body image registration. Typical dosimetric endpoints were used to assess the accuracy of this approach. Results: The prostate moved 0.4–0.7 cm superior in 38% days, > 0.8 cm superior in 19%, 0.4–0.7 cm posterior in 12%, and less than 0.3 cm in all directions in 31%. Of these days, 12 (65%) of the daily dose to the 95% of the prostate was greater than 98% of the prescribed dose, 4 (24%) in the range of 93% to 97%, and 2 (11%) less than 90% of the prescription dose. Among these days, the pelvic lymph node volume received 100% of the planned dose. Conclusion: The MAP adaptive approach is a clinically feasible strategy. Verification plan calculated with daily MV‐CBCT as a dosimetric monitoring tool provides patient specific dose guidance.

SU-G-JeP1-10: Feasibility of CyberKnife Tracking Using the Previously-Implanted Permanent Brachytherapy Seed Cloud

PURPOSE Robotic radiosurgery is a salvage treatment option for patients with recurrent prostate cancer. We explored the feasibility of tracking the bolus of permanent prostate implants (PPI) using image recognition software optimized to track spinal anatomy. METHODS Forty-five inert iodine seeds were implanted into a gelatin-based prostate phantom. Four superficial gold seeds were inserted to provide ground-truth alignment. A CT scan of the phantom (120 kVp, 1 mm slice thickness) was acquired and a single-energy iterative metal artifact reduction (MAR) algorithm was used to enhance the quality of the DRR used for tracking. CyberKnife treatment plans were generated from the MAR CT and regular CT (no-MAR) using spine tracking. The spine-tracking grid was centered on the bolus of seeds and resized to encompass the full seed cloud. A third plan was created from the regular CT scan, using fiducial tracking based on the 4 superficial gold seeds with identical align-center coordinates. The phantom was initially aligned using the fiducial-tracking plan. Then the MAR and no-MAR spine-tracking plans were loaded without moving the phantom. Differences in couch correction parameters were recorded in the case of perfect alignment and after the application of known rotations and translations (roll/pitch of 2 degrees; translations XYZ of 2 cm). RESULTS The spine tracking software was able to lock on to the bolus of seeds and provide couch corrections both in the MAR and no-MAR plans. In all cases, differences in the couch correction parameters from fiducial alignment were <0.5 mm in translations and <1 degree in rotations. CONCLUSION We were able to successfully track the bolus of seeds with the spine-tracking grid in phantom experiments. For clinical applications, further investigation and developments to adapt the spine-tracking algorithm to optimize for PPI seed cloud tracking is needed to provide reliable tracking in patients. One of the authors (MD) has received research support and speaker honoraria from Accuray.

Does enrollment setting influence patient attributes and outcomes in RTOG prostate cancer trials

4607 Background: The external validity of randomized trials (generalizability) has been called into question following the finding that patients treated on clinical trials vary substantially from patients treated in the usual care setting. The purpose of this secondary analysis is to examine whether results of prostate randomized trials within the RTOG differ according to enrollment setting. METHODS 4,154 patients accrued into one of 4 RTOG trials between 1987-1999 were included in this analysis. There were 224 North American institutions enrolling in one or more trials. Patient attributes were compared by enrollment settings, controlling for trial. Survival regression models stratified by trial and including patient attributes were used to evaluate survival differences by enrollment setting. RESULTS Academic institutions enrolled 36% of patients; community centers enrolled 49%; CCOPs enrolled 14%, and VHAs enrolled 2%. With respect to patient attributes, men from Academic and VHA centers tended to have better performance status, black men were less frequently enrolled from non-CCOP community institutions, and Gleason scores tended to be higher in men from CCOPs. Age at diagnosis did not differ materially by enrollment setting. Adjusted for patient attributes, survival by enrollment setting did not differ significantly (Table). CONCLUSIONS Attributes of prostate cancer patients enrolled in these RTOG trials Phase III differed modestly according to enrollment site type. Accounting for these differences, overall survival did not depend on the type of institution from which patients were enrolled. These findings support the external validity of RTOG prostate trials.This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). [Table: see text].