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Biomedical subjects

Gregory Merrick

Publications and source records attributed to Gregory Merrick.

26 records · Page 2Linked to original sources

Interpretation of pre- versus postimplant TRUS images.

In order to summarize the inter-observer variability of pre- and postimplant TRUS image interpretation. Ten patients treated with Pd-103 brachytherapy were studied. Preimplant prostatevolumes ranged from 21 to 51 cm3. The number of sources implanted ranged from 74 to 155, and the number of sources per cm3 prostate volume ranged from 3.0 to 4.3. A set of transverse images (6 MHz) were taken immediately prior to and following source placement. Original printer images were sent to four investigators and the prostate outlined independently on a cellophane overlay. The overlays were digitized into a Varian MMS 7.0 treatment planning system (Charlottesville, VA) for volume determinations. There was moderate interobserver variability in TRUS volume determination, accentuated for the postimplant images. The standard deviations varied from 2% to 13% of the mean (median: 7%) for preimplant volumes, versus 7% to 32% (median: 13%) for postimplant volumes. Interobserver prostatic edge (border) localization variability was greatest at the base and apex, with closer agreement along the posterior border. For preimplant images, the majority of edge points were within 1.0 mm of the mean. At each coordinate, with the exception of the anterior base, the majority of points were within 2.0 mm of the mean. In general, border identification variability was greater in the post implant images. While all prostate imaging modalities suffer from interobserver variability, preimplant and postimplant TRUS appears capable of consistently determining prostatic volume and borders. It appears that intraoperative TRUS-based dosimetry is a practical goal, provided that seed location coordinates can be added to the prostatic edge information derived from TRUS images.

Brachytherapy↗

The effect of interobserver differences in post-implant prostate CT image interpretation on dosimetric parameters.

The purpose of this study was to clarify where observers differ in their interpretation of CT scans, and to relate those differences to clinically relevant dosimetric parameters. Twenty unselected patients treated with I-125 or Pd-103 brachytherapy at the Veterans Affairs Puget Sound Health Care System (VAPSHCS) in 2001 were studied. Patients were implanted with I-125 (7 patients, 0.87 mCi/source) or Pd-103 (13 patients, 2.54 U/source). The number of I-125 sources implanted ranged from 52 to 78. The number of Pd-103 sources implanted ranged from 58-144. Post-implant 3 mm CT images were imported into a laptop running Varian Variseed and sent to the four physician investigators, who outlined the prostate independently. Investigators were not coached specifically for this study, beyond their having read prior reports regarding prostate volume determinations. There was moderate interobserver variability in CT volume determination, with the standard deviations as a percent of the mean ranging from 9% to 29% (median: 17%). An average of 14% of implants (range: 5%-20%) would have been judged inadequate based on a minimum V100 of 80%, versus 24% of implants (range: 5%-45%) being judged inadequate based on a minimum D90 of 90% of prescription dose. The greatest variability was seen in prostate length (median standard deviation: 0.57 cm), due to vagaries in base and apical localization. However, the prostatic width and thickness also varied substantially between observers, with median standard deviations of 0.24 and 0.32 cm, respectively. Treatment margin variability was greatest at the anterior border, with a median standard deviation of 0.21 cm +/- 0.10. We believe that CT-based dosimetry, while influenced by CT interpretation, still provides useful general dosimetric calculations, that are likely to be reproducible enough to provide clinically useful information between institutions. The V100 and TMs are less influenced by interobserver CT interpretation variability than is the D90, and may be better suited as interinstitutional quality indices.

Humans↗

Clinical correlates of high intraprostatic brachytherapy dose volumes.

PURPOSE: To determine if high intraprostatic dose regions correlate with postimplant urinary or rectal morbidity, potentially providing some objective basis for recommendations regarding dose homogeneity. METHODS: Eighty-two patients with 1997 AJC clinical stage T1c-T2a prostatic carcinoma (Gleason Grade 2-6, PSA 4-10 ng/ml) were randomized to implantation with 125I (144 Gy) vs. 103Pd (125 Gy, NIST-1999). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. The 125I source strength ranged from 0.4 to 0.89 mCi (median: 0.55 mCi), and the 103Pd source strength ranged from 1.3 to 1.6 mCi (median: 1.5 mCi). The total number of 125I sources implanted ranged from 30 to 186 (median: 69). The total number of 103Pd sources ranged from 60 to 182 (median: 106). A postimplant computed tomography scan was obtained within 2 to 4 hours postimplant. The V100, V200, and V300s were calculated as the percent of the total prostate receiving greater than two, three, or four times the prescription dose, respectively. Treatment-related morbidity was monitored by mailed questionnaires using standard American Urologic Association and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12, and 24 months. The DeltaAUA score was taken as the AUA (American Urologic Association) score at the time of interest minus the preimplant score. RESULTS: The mean V100, V200, and V300 were 90% (+/-8%), 35% (+/-13%), and 14% (+/-7%), respectively. Higher-dose parameters (V300) correlated more closely with each other than lower-dose parameters. The DeltaAUA at 1 month had increasing association with higher-dose volumes, the closest association being with V300. However, there was substantial scatter in the data, as evidenced by the low r values. There was no correlation between high-dose volumes and DeltaAUA at 12 months. Urinary morbidity scores were greatest at the 1-month time point, with no correlation between urinary morbidity and high-dose volumes. There was no correlation between rectal morbidity and high-dose volumes. CONCLUSION: Expending substantial effort to monitor and modify higher-dose volumes, at least in the setting of modified peripheral loading patterns, is unlikely to substantially decrease implant-related morbidity.

Brachytherapy↗

Prostate brachytherapy in obese patients.

PURPOSE: To identify and illustrate the potential problems with brachytherapy in obese patients. METHODS AND MATERIALS: Three patients with body mass index greater than 30 were treated with prostate brachytherapy. Transrectal ultrasound (TRUS) was performed using a 6.0-MHz Siemens Sonoline Prima ultrasound machine and a Barzell-Whitmore stepper unit. The patients' weight required use of an accessory table support. RESULTS: Once set up, there was ample room to maneuver, providing that the patient's legs were abducted fully. TRUS imaging of the prostate was unaffected by patients' obesity. The amount of periprostate adipose tissue visualized on TRUS appeared to be no different than that noted in nonobese patients. Similarly, there was no increased distance between the prostate and rectal surface, either on preimplant CT or transverse TRUS. To date, our experience is that the perineal skin to prostate distance was not so great that standard 20-cm applicator needles could not be used. For the 2 sub-350-pound patients who could be imaged on our CT scanner, postimplant target coverage (V100) was 88% and 95%. CONCLUSIONS: Standard TRUS and brachytherapy needles are sufficient to implant even the largest patients.

Brachytherapy↗

Modification of prostate implants based on postimplant treatment margin assessment.

PURPOSE: To quantify the extent of additional source placement needed to perfect an implant after execution by standard techniques, assuming that uniform 5 mm treatment margins (TMs) is the criteria for perfection. MATERIALS AND METHODS: Ten consecutive, unselected patients treated with 1-125 brachytherapy were studied. Source placement is planned just inside or outside of the prostatic margin, to achieve a minimum 5 mm TM and a central dose of 150%-200% of the prescription dose. The preimplant prostate volumes ranged from 24 to 85 cc (median: 35 cc). The number of sources implanted ranged from 48 to 102 (median: 63). Axial CT images were acquired within 2 h postoperatively for postimplant dosimetry. After completion of standard dosimetric calculations, the TMs were measured and tabulated at 45 degrees intervals around the prostate periphery at 0.0, 1.0, 2.0, and 3.0 cm planes. Sources were then added to the periphery to bring the TMs to a minimum of 5 mm at each measured TM, resulting in a modified implant. All margin modifications were done manually, without the aid of automated software. RESULTS: Patients' original (unmodified) D90s ranged from 111% to 154%, with a median of 116%. The original V100s ranged from 94% to 99%, with a median of 96%. No patient required placement of additional sources to meet a minimum D90 of 90% or a minimum V100 of 80%. In contrast, patients required from 7 to 17 additional sources (median: 11) to achieve minimum 5 mm TMs around the entire prostatic periphery. Additional sources equaled from 12% to 24% of the initial number of sources placed (median: 17%). By adding sufficient peripheral sources to bring the TMs to a minimum 5 mm, patients' average V100 increased from 96% to 100%, and the average D90 increased from 124% to 160% of prescription dose. In the course of achieving a minimum 5 mm TM, the average treatment margin for all patients combined increased from 5.5 to 9.9 mm. The number of sources needed to bring the TMs to a minimum 5 mm was loosely correlated with the preimplant prostate volume and the change in prostate volume from implant-related swelling. Adding sufficient sources to achieve minimum 5 mm TMs increased the prostate volume receiving greater than 200% of the prescription dose (V200) from 39% to 58%, and increased the average urethral point dose (2.00 cm inferior to the bladder) from 154% to 171% of the 144 Gy prescription isodose. CONCLUSIONS: Minimum 5 mm TMs are not uniformly achieved with current implant techniques. It seems that doing so, even in experienced hands, will require a reappraisal of our implant techniques, or the addition of intraoperative dosimetric analysis with the capacity to substantially modify the implant with extra sources.

Brachytherapy↗

The prognostic significance of Gleason pattern 5 in prostate cancer patients treated with Pd 103 plus beam radiation therapy.

BACKGROUND: There is little clinical information specifically regarding the clinical significance of Gleason pattern 5 in prostate biopsies. Accordingly, we have analyzed the effect of pattern 5 cancer on the prognosis of prostate cancer treated with Pd-103 brachytherapy. METHODS: Intermediate-risk patients with a Gleason score of 7 or higher and/or a prostate-specific antigen level of 10-20 ng/mL and whose biopsy slides were available for review were treated on a randomized trial. The regimens consisted of implantation with Pd 103 (90 vs 115 Gy [National Institute of Standards and Technology; NIST-1999]), combined with 44 Gy versus 20 Gy of supplemental beam radiation, respectively. Beam radiation was delivered with a four-field arrangement, designed to cover the prostate and seminal vesicles with a 2-cm margin (reduced to 1.0 cm posteriorly). Isotope implantation was per formed by standard techniques, using a modified peripheral loading pattern. All prostate biopsy specimens were reviewed for Gleason score by one investigator (L. T.). Along with assignment of a Gleason score based on established criteria, the presence of any pattern 5 cancer was separately noted and photographed for future review. Freedom from biochemical failure was defined as a serum prostate-specific antigen level < or = 0.5 ng/mL at last follow-up. Four of the 156 patients had insufficient PSA follow-up for inclusion, leaving 152 patients for cancer control analysis. RESULTS: Overall actuarial biochemical freedom from failure was 86% at 3 years, with 20 patients having experienced biochemical failure. Patients with or without Gleason pattern 5 cancer in their biopsy specimen had similar overall biochemical control. There was no obvious trend toward poorer overall biochemical cancer control in patients with pattern 5 cancer, regardless of whether the pretreatment prostate-specific antigen was less than or greater than 10 ng/mL. Of the 17 patients with biochemical failure, clinically evident bone metastases has developed in five. Three of these five patients who had a positive bone scan had pattern 5 cancer in their biopsy. CONCLUSIONS: Although the presence of pattern 5 disease may be a risk factor for early systemic failure, we are encouraged that high-dose, brachytherapy-based treatment seems to provide a high likelihood of biochemical cancer control, even in patients with the highest-grade cancer.

Antineoplastic Agents, Hormonal↗

Extraprostatic seed placement and its effect on seed loss.

PURPOSE: The purpose of this study was to examine the relationship between extraprostatic seed placement and seed loss in a cohort of patients who had underwent both computed tomographic (CT) and magnetic resonance (MR) scans at day 0 and day 30 following brachytherapy. MATERIALS AND METHODS: Twenty-two patients with 1997 AJC clinical stage T1-T2 prostatic carcinoma were implanted with nonstranded I 125. Patients were selected solely by having a prostate volume between 15 and 60 cc and a willingness to return for 30-day follow-up CT and MR scans. The total number of I-125 sources implanted on day 0 ranged from 50 to 104 (median: 70). Preplan treatment planning methods have been previously described in detail: a modified peripheral loading pattern and treatment margins of 5-10 mm were used. Noncontrast postimplantation CT and MR scans were obtained 1-4 hours after implantation on day 0. The total seed count on days 0 and 30 was verified by plain radiograph. Pelvic MR (T1) images were registered with the CT images in the Varian planning system, using bony landmarks. The number of extracapsular seeds in each quadrant of the circumference was then totaled for each patient. A second set of plain radiographs (for seed counting), as well as CT and MR scans, were obtained 30 days after implantation (day 30) and were similarly analyzed. RESULTS: The number of extraprostatic seeds at day 0 ranged from 13 to 35, making up 17%-48% (median: 34%) of the total number implanted. Of the 22 patients, 10 lost one or more seeds between the implantation day and the 1-month follow-up. The mean number of seeds lost was 1.1 (+/- 1.7). There was no apparent relationship between the percent of extraprostatic seeds and the number of seeds lost. There was no apparent relationship between seed loss and number of seeds less than 3 mm or greater than 3 mm from the prostatic capsule. CONCLUSIONS: We have shown here that with CT and MR seed localization, extraprostatic seed placement does not appear to substantially increase the likelihood of seed loss after the procedure.

Brachytherapy↗

I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial.

BACKGROUND: We tested the hypothesis that the shorter half-life of Pd-103 versus I-125 results in different late radiation-related morbidities following prostate brachytherapy. METHODS: As of June 14th, 2002, 352 of a planned total of 600 patients with 1997 American Joint Committee on Cancer (AJCC) clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, PSA 4-10 ng/mL) had been randomized to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Treatment-related morbidity was monitored by questionnaires based on standard American Urologic Association (AUA) and Radiation Therapy Oncology Group (RTOG) criteria that were mailed at 1, 3, 6, 12, 18, and 24 months after implant. The use of alpha-blockers to relieve obstructive symptoms was not controlled for but was noted at each follow-up point. All patients reported here had a minimum follow-up of 2 years. Dosimetric parameters analyzed included the V100, which was defined as the percentage of the postimplant prostate volume covered by 100% of the prescription dose. Rectal doses were expressed as the R100, defined as the rectal volume (cc) that received at least 100% of the prescription dose. Statistical comparisons were by Student's unpaired t-test at specified follow-up times. RESULTS: The AUA scores peaked at the 1-month postimplant time point for both isotopes and gradually declined. The difference in AUA scores between patients who received I-125 versus those who received Pd-103 was greatest at 1 and 6 months following implantation. At 1 month, I-125 patients had a mean AUA score of 14.8 (+/-9.5) compared with 18.6 (+/-9.8) for the Pd-103 patients (P = 0.0009). By 6 months, mean AUA scores for the I-125 patients had decreased to 12.0 (+/-9.1) compared with 9.9 (+/-8.7) for the Pd-103 patients (P = 0.04). The use of alpha-blockers was similar between groups at all time points. Radiation proctitis (persistent bleeding) occurred in 29 of 314 patients (9%). There was an overall trend toward more proctitis in I-125 patients (P = 0.21). However, only four of the 163 patients (2%) with an R100 below the recommended 1.0 cc developed bleeding, which did not differ between isotopes (P = 0.49). DISCUSSION: Patients treated with Pd-103 had more intense radiation prostatitis in the first month after implantation, but they recovered from their radiation-related symptoms sooner than I-125 patients, consistent with palladium's shorter half-life. The trend toward more proctitis in the I-125 patient group likely reflects their higher R100 values due to less rapid dose fall-off that can be overcome with judicious treatment planning and implant execution.

Aged↗