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Gregory Merrick

Publications and source records attributed to Gregory Merrick.

At least 19 recordsLinked to original sources
PubMed2006

15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience.

PURPOSE: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy. METHODS AND MATERIALS: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I(125) or Pd (103) brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots. RESULTS: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D'Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% (p = 0.002). CONCLUSIONS: I(125) or Pd(103) brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

Aged↗
PubMed2005

Rectal fistulas after prostate brachytherapy.

PURPOSE: To compare the rectal and prostatic radiation doses for a prospective series of 503 patients, 44 of whom developed persistent rectal bleeding, and 2 of whom developed rectal-prostatic fistulas. METHODS AND MATERIALS: The 503 patients were randomized and treated by implantation with 125I vs. 103Pd alone (n = 290) or to 103Pd with 20 Gy vs. 44 Gy supplemental external beam radiotherapy (n = 213) and treated at the Puget Sound Veterans Affairs Medical Center (n = 227), Schiffler Cancer Center (n = 242) or University of Washington (n = 34). Patients were treated between September 1998 and October 2001 and had a minimum of 24 months of follow-up. The patient groups were treated concurrently. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urological Association and Radiation Therapy Oncology Group criteria, at 1, 3, 6, 12, 18, and 24 months. Patients who reported Grade 1 or greater Radiation Therapy Oncology Group rectal morbidity were interviewed by telephone to clarify details regarding their rectal bleeding. Those who reported persistent bleeding, lasting for >1 month were included as having Grade 2 toxicity. Three of the patients with rectal bleeding required a colostomy, two of whom developed a fistula. No patient was lost to follow-up. The rectal doses were defined as the rectal volume in cubic centimeters that received >50%, 100%, 200%, or 300% of the prescription dose. The rectum was considered as a solid structure defined by the outer wall, without attempting to differentiate the inner wall or contents. RESULTS: Persistent rectal bleeding occurred in 44 of the 502 patients, 32 of whom (73%) underwent confirmatory endoscopy. In univariate analysis, multiple parameters were associated with late rectal bleeding, including all rectal brachytherapy indexes. In multivariate analysis, however, only the rectal volume that received >100% of the dose was significantly predictive of bleeding. Rectal fistulas occurred in 2 patients (0.4%), both of whom had received moderate rectal radiation doses and extensive intervention for rectal bleeding. CONCLUSION: Partly on the basis of data from others and data presented here, we believe that the incidence of rectal fistulas can be much lower than in our series. High rectal radiation doses should be avoided a priori, to minimize the likelihood of rectal bleeding, and hence the likelihood that invasive procedures will be performed.

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PubMed2005

Effect of post-implant edema on prostate brachytherapy treatment margins.

PURPOSE: To determine if postimplant prostate brachytherapy treatment margins calculated on Day 0 differ substantially from those calculated on Day 30. METHODS: Thirty patients with 1997 American Joint Commission on Cancer clinical stage T1-T2 prostatic carcinoma underwent prostate brachytherapy with I-125 prescribed to 144 Gy. Treatment planning methods included using loose seeds in a modified peripheral loading pattern and treatment margins (TMs) of 5-8 mm. Postimplant plain radiographs, computed tomography scans, and magnetic resonance scans were obtained 1-4 hours after implantation (Day 0). A second set of imaging studies was obtained at 30 days after implantation (Day 30) and similarly analyzed. Treatment margins were measured as the radial distance in millimeters from the prostate edge to the 100% isodose line. The TMs were measured and tabulated at 90 degrees intervals around the prostate periphery at 0.6-cm intervals. Each direction was averaged to obtain the mean anterior, posterior, left, and right margins. RESULTS: The mean overall TM increased from 2.6 mm (+/-2.3) on Day 0 to 3.5 mm (+/-2.4) on Day 30. The mean anterior margin increased from 1.2 mm on Day 0 to 1.8 mm on Day 30. The posterior margin increased from 1.2 mm on Day 0 to 2.8 mm on Day 30. The lateral treatment margins increased most over time, with mean right treatment margin increasing from 3.9 mm on Day 0 to 4.7 mm on Day 30. CONCLUSION: Treatment margins appear to be durable in the postimplant period, with a clinically insignificant increase from Day 0 to Day 30.

Brachytherapy↗
PubMed2005

High-dose regions versus likelihood of cure after prostate brachytherapy.

PURPOSE: To analyze the effect of high-dose regions on biochemical cancer control rates after prostate brachytherapy. METHODS AND MATERIALS: Patients with 1997 American Joint Committee on Cancer clinical Stage T1c-T2a prostate carcinoma (Gleason grade 5-6, prostate-specific antigen level 4-10 ng/mL) were randomized to implantation with 125I (144 Gy) vs. 103Pd (125 Gy, National Institute of Standards and Technology 1999). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Of the 313 patients entered in the protocol, 270 were included in this analysis. 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). CT was performed within 4 h after implantation. The dosimetric parameters analyzed included the percentage of the postimplant prostate volume covered by the 100%, 150%, 200%, and 300% prescription dose (V100, V150, V200, and V300, respectively). The median time to the last follow-up for patients without failure was 2.7 years. Freedom from biochemical failure was defined as a serum prostate-specific antigen level of < or =0.5 ng/mL at last follow-up. Patients were censored at last follow-up if their serum prostate-specific antigen level was still decreasing. RESULTS: The mean V100, V150, V200, and V300 value was 90% (+/-8%), 63% (+/-14), 35% (+/-13%), and 14% (+/-7%), respectively. Patients with a V100 of > or =90% had a 3-year freedom from biochemical failure rate of 96% vs. 87% for those with a V100 of <90% (p=0.0029). Overall, patients with more high-dose regions had a greater chance of biochemical control. However, when only patients with a V100 of > or =90% were analyzed, no relationship was found between higher dose regions and the likelihood of cancer control. This lack of effect on biochemical control was apparent for both isotopes. CONCLUSION: High-dose regions do not appear to affect cancer control rates, as long as >90% of the prostate volume is covered by the prescription dose.

Brachytherapy↗
PubMed2005

20 Gy versus 44 Gy supplemental beam radiation with Pd-103 prostate brachytherapy: preliminary biochemical outcomes from a prospective randomized multi-center trial.

BACKGROUND AND PURPOSE: While favorable results are achieved with combined modality irradiation, there has never been a rigorous study of the need for supplemental beam. The study reported here compares clinical outcomes with substantially different external beam radiation doses. Similar to classic randomized Wilm's tumor studies from the 1980s, the intention of the trial design was to decrementally test the need for beam radiation. PATIENTS AND METHODS: As of June 2000, 165 of a planned 600 patients with 1997 AJC clinical stage T1c-T2a prostatic carcinoma, Gleason grade 7-10 and/or PSA 10-20 ng/ml, were treated on a randomized protocol comparing 44 versus 20 Gy pre-implant supplemental beam radiation, combined with Pd-103, 90 versus 115 Gy, respectively (NIST-1999). Freedom from biochemical failure was defined as a serum PSA</=0.5 ng/ml at last follow-up. Patients were censored at last follow-up if their serum PSA was still decreasing. Patients whose serum PSA nadired at a value >0.5 ng/ml were scored as failures at the time at which their PSA nadired. The follow-up period for non-failing patients ranged from 0.5 to 4.9 years (median: 2.9 years). Accrual of 566 patients was achieved in October 2004. The study was closed at that time because of slowing accrual, due in part to the findings reported here. RESULTS: The overall actuarial freedom from biochemical progression at 3 years is 85%, with 59 patients followed beyond 3 years. A total of 21 patients have developed biochemical failure, 12 treated with 20 Gy and nine treated with 44 Gy. There were no clinically evident local failures. The actuarial biochemical freedom-from-failure rate at 3 years was 83% for 20 Gy patients versus 88% for 44 Gy patients (P=0.64). For 112 patients with a pre-treatment PSA<10 ng/ml, the 3-year freedom from progression was 84% in patients receiving 20 Gy beam radiation versus 94% in those who received 44 Gy beam (P=0.16). For 47 patients with a pre-treatment PSA>10 ng/ml, the 3-year freedom from progression was 82% in patients receiving 20 Gy beam radiation versus 72% in those who received 44 Gy beam (P=0.38). CONCLUSIONS: The randomized data presented here suggests that the likelihood of biochemical cure is similar with standard (44 Gy) or lower dose (20 Gy) supplemental beam radiation. Since the biological effect of 20 Gy external beam radiation is likely to be small, we interpret these preliminary results to suggest that supplemental beam radiation is unnecessary, in the setting of a high degree of prostate coverage by the brachytherapy prescription dose. With closure of this study, we have begun treating intermediate and high risk patients on a prospective randomized comparison of Pd-103 with 20 versus 0 Gy supplemental beam radiation.

Aged↗
PubMed2004

Perirectal seeds as a risk factor for prostate brachytherapy-related rectal bleeding.

PURPOSE: To correlate rectal wall doses and perirectal seed numbers with late rectal bleeding after prostate brachytherapy. METHODS AND MATERIALS: We studied 148 patients randomized to implantation with I-125 vs. Pd-103 at the VA Puget Sound HCS from 1998 through 2001 and for whom postimplant dosimetry was available. Implants were performed by standard techniques, using a modified peripheral loading pattern. A postimplant computed tomography (CT) scan (3 mm slice thickness) was obtained 1-4 h after implantation. Rectal doses were expressed as the R100, R200, and R300, defined as the rectal volume (cc) that received more than 100%, 200%, or 300% of the prescription dose, respectively. The rectum was considered to be a solid structure defined by the outer wall, without attempting to differentiate the inner wall or contents. In addition to conventional dose parameters, each patient's postimplant CT scan was reviewed for the number of seeds within 0, 0.1-2, and 2.1-4 mm of the outer rectal wall. The proximal edge of the seed was used for distance determinations from the outer rectal wall. Patients who reported Grade 1 or higher Radiation Therapy Oncology Group morbidity were contacted by telephone to obtain more details regarding their rectal bleeding. Those who reported persistent bleeding lasting for more than 1 month were categorized as Grade 2. RESULTS: Patients had a wide range of rectal wall doses, with R100 values ranging from 0.0 to 10.4 cc (median, 0.95 cc). Similarly, the number of perirectal seeds within 0.0 to 2.0 mm of the rectum varied widely, ranging from 0 to 12 seeds (median: 1 seed). Seven patients (7 of 144 = 5%) developed persistent rectal bleeding, one of whom required a colostomy. Both rectal radiation doses and the number of perirectal seeds were higher in patients with persistent rectal bleeding. The number of perirectal seeds < or =2.0 mm of the rectal wall was higher in patients with rectal bleeding (p = 0.037), but the number of seeds 2-4 mm from the wall were not related (p = 0.72). In multivariate regression analysis including prostatic D90 (the dose that covers 90% of the postimplant prostate), preimplant transrectal ultrasound volume, R300, and the number of seeds < or =2 mm from the rectal wall as independent variables, only the R300 was statistically significantly associated with the likelihood of persistent rectal bleeding (p = 0.025). CONCLUSION: A limited number of errant perirectal sources in itself does not appear to place patients at increased risk of rectal bleeding, providing that the overall rectal wall doses are within acceptable values.

Brachytherapy↗
PubMed2004

Factors predictive of rectal bleeding after 103Pd and supplemental beam radiation for prostate cancer.

PURPOSE: To evaluate the contribution of various clinical and radiation treatment parameters to the likelihood of late rectal bleeding after brachytherapy plus supplemental beam radiation (EB). METHODS: A total of 161 intermediate risk patients, with Gleason score 7 or higher and/or PSA 10-20 ng/ml randomized to implantation with (103)Pd (90 versus 115 Gy) with 44 versus 20 Gy EB (2 Gy/day) were studied. 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 performed by standard techniques, using a modified peripheral loading pattern. A postimplant CT scan (3 mm slice thickness) was obtained 1-4 h after implantation. Dose volume histograms of the prostate and rectum were calculated using the outer prostatic and rectal margins identified on CT scan by one investigator (KW). Rectal doses were expressed as the R100, R200, and R300, defined as the rectal volume (cc) that received at least 100%, 200%, or 300% of the prescription dose, respectively. External beam doses were expressed as EB75% (cc)-the volume of rectum that received 75% of the beam prescription dose. Treatment-related rectal morbidity was monitored by mailed questionnaires, using Radiation Therapy Oncology Group (RTOG) criteria, at 1, 3, 6, 12, 24, and 36 months. Patients who reported Grade 1 or higher RTOG morbidity were contacted by telephone to obtain more details regarding their rectal bleeding. RESULTS: In univariate analysis, rectal bleeding was statistically related to the R100, R200, and R300 values, with p-values of 0.0055, 0.0007, and 0.012, respectively. Bleeding was not related to gap times, prostate size, patient age, V100 or D90 values. The EB75% values were similar in 44 Gy patients with or without late bleeding. CONCLUSION: Considering the potential severity of rectal morbidities and their relationship to implant dose, we urge our colleagues to routinely monitor the rectal implant doses of their own patients to make sure that such doses are kept within an accepted range.

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PubMed2004

Chronic pelvic pain following prostate brachytherapy: a case report.

PURPOSE: To alert physicians and potential patients that chronic postimplant pelvic pain syndromes can occur, and that dosimetric parameters (i.e., implant technique) may predispose patients to it. METHODS AND MATERIALS: The authors are currently following 3 prostate brachytherapy patients with what appear to be chronic radiation-related pelvic pain, variously exacerbated by urination or perineal pressure. The 3 patients were identified in the course of routine follow-up, and do not represent a concerted attempt to identify such patients from a larger group of patients being followed by the authors. Three control groups of 10 patients each treated with (125)I, (103)Pd, or (103)Pd + external beam radiation and with no reported dysuria at 6 months postimplant were taken from two ongoing prospective trials. The 3 patients reported here were each administered a brief questionnaire regarding the effect of their urinary pain on daily activities. RESULTS: Patients with chronic pain tended to have high central prostatic doses, at least on some planes. Maximal, mean, and median urethral doses were higher for patients with chronic pain, but there was some overlap with control patients. The prostate V100s were similar between patients with chronic pain and controls, but there was a trend toward higher V200s and V300s in pain syndrome patients. CONCLUSION: Recalcitrant brachytherapy-related pelvic pain is an uncommon occurrence that may be partly related to higher central prostatic doses.

Aged↗
PubMed2004

Medical malpractice of prostate brachytherapy.

PURPOSE: To summarize the basis for brachytherapy-associated legal complaints. METHODS AND MATERIALS: The cases summarized here were those worked on by one author (KW) from 1992 through 2002. Summary information about cases is kept solely for the purpose of informing opposing counsel regarding past experience as a defendant or expert witness. No information summarized here is kept for medical research purposes. KW was the defendant in three cases, and an expert witness in the remaining 10 cases. RESULTS: Eleven cases were initiated due to a prostatic-rectal fistula--an abnormal communication between the prostatic urethra and rectum formed because of breakdown of irradiated tissue. Of the cases not involving a fistula, one was initiated due to chronic urinary burning, and the other arose from a patient identification mix-up, such that the plaintiff was treated with the implant planned for another patient. The principal physician defendant(s), after pre-trial winnowing, was the radiation oncologist alone in eight cases and the radiation oncologist and the urologist in five cases. In no case was a urologist named as a defendant without the radiation oncologist. None of the eleven rectal fistula cases involved an egregious seed placement error. Instead, plaintiff attorneys typically claimed breach of standard for care for what most physicians would likely consider to be variations within the standard of care. CONCLUSION: Prostate brachytherapists should brace themselves for the likelihood of more lawsuits. In addition to fistulas, plaintiff attorneys are likely to devise more bases for lawsuits in the future.

Brachytherapy↗
PubMed2004

Epididymitis after prostate brachytherapy.

OBJECTIVES: To analyze the incidence, time-course, and potential predisposing factors for what was clinically diagnosed as postimplant epididymitis. METHODS: Of 517 patients randomized and treated on two treatment protocols, with a planned total accrual of 1200, 5 patients were identified who developed clinically diagnosed epididymitis after iodine-125 or pallidium-103 prostate brachytherapy. Implants were performed by standard techniques, using a modified peripheral loading pattern. Perioperative antibiotics (cefazolin and ciprofloxacin) were given to 258 patients, according to physician preference. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urological Association (AUA) and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12, and 24 months. Patients who did not respond to the mailed questionnaires were interviewed by telephone. Although the patients were not queried specifically regarding epididymitis, its occurrence was noted when discovered in the course of follow-up examinations. RESULTS: Postimplant epididymitis occurred in 5 (1%) of 517 consecutive brachytherapy patients. None of the 5 patients had had a prior history of orchitis, epididymitis, vasectomy, or preimplant catheterization. The symptoms of epididymitis first appeared at 4, 7, 10, 150, and 300 days after implantation. Patients with epididymitis had prostate volumes, preimplant AUA scores, and ages typical of other implant patients. No association was apparent between postimplant epididymitis and the degree of implant-related prostate swelling or the number of seeds implanted. Only the preimplant AUA score predicted for epididymitis, but 2 of the 5 patients had low scores. Only 1 (0.4%) of the 258 patients who received perioperative antibiotics developed epididymitis, and 4 (1.5%) of the 259 patients with prophylactic antibiotics developed epididymitis. CONCLUSIONS: Epididymitis is an uncommon postimplant complication occurring in 1% of a large patient cohort. That epididymitis patients had greater preimplant AUA scores is consistent with a retrograde infection route, at least in some cases.

Adenocarcinoma↗
PubMed2003

125I versus 103Pd for low-risk prostate cancer: preliminary PSA outcomes from a prospective randomized multicenter trial.

PURPOSE: To compare prostate cancer control rates in patients who received (125)I vs. (103)Pd. MATERIALS AND METHODS: Of a planned total of 600 patients with 1997 American Joint Committee on Cancer clinical Stage T1c-T2a prostate carcinoma (Gleason score 5-6, prostate-specific antigen [PSA] 4-10 ng/mL), 126 were randomized to implantation with (125)I (144 Gy) vs. (103)Pd (125 Gy). The prostate biopsies were reviewed for Gleason score by one of us (L.T.). A single manufacturer of (125)I sources (Model 6711, Amersham, Chicago, IL) and (103)Pd sources (Theraseed, Theragenics, Buford, Georgia) was used. Isotope implantation was performed with standard techniques, using a modified peripheral loading pattern. Of a total of 126 patients randomized, 11 were excluded, leaving 115 randomized patients for this analysis. Twenty patients received a short course of preimplant hormonal therapy, none of whom continued hormonal therapy after their implant procedure. Postimplant CT was obtained 2-4 hours after implantation. The dosimetric parameters analyzed included the percentage of the postimplant prostate or rectal volume covered by the prescription dose (V(100)) and the dose that covered 90% of the postimplant prostate volume (D(90)). Freedom from biochemical failure was defined as a serum PSA level < or =0.5 ng/mL at last follow-up. Patients were censored at last follow-up if their serum PSA level was still decreasing. Patients whose serum PSA had reached a nadir at a value >0.5 ng/mL were scored as having failure at the time at which their PSA had reached a nadir. The follow-up period for patients without failure ranged from 2.0 to 4.9 years (median 2.9). Freedom-from-failure curves were calculated by the Kaplan-Meier method. Differences between groups were determined by the log-rank method. RESULTS: The actuarial biochemical freedom-from-failure rate at 3 years was 89% for (125)I patients vs. 91% for (103)Pd patients (p = 0.76). The 3-year biochemical freedom-from-failure rate for patients with a D(90) <100% of the prescription dose was 82% vs. 97% for patients with a D(90) > or =100% of the prescription dose (p = 0.01). Similarly, the 3-year biochemical freedom-from-failure rate for patients with a V(100) <90% of the prescription dose was 87% vs. 97% for patients with a V(100) > or =90% of the prescription dose (p = 0.01). The effect of the dosimetric parameters on biochemical control was most pronounced for (125)I, but also apparent for (103)Pd. CONCLUSIONS: The 3-year actuarial biochemical control rates for low early-stage prostate cancer are similar after (125)I and (103)Pd.

Aged↗
PubMed2003

Isodose patterns in patients with inadequate prostate brachytherapy coverage.

PURPOSE: The development of a practical, real-time dosimetry system should result in improved implant dose distributions and higher prostate cancer control rates. Our purpose here is to demonstrate that intraoperative isodose reconstruction in relation to the seed distribution, even without accurate registration with the prostatic volume, can likely identify an inadequate implant intraoperatively and guide corrective seed placement. METHODS AND MATERIALS: A total of 102 Pd-103 implants performed by standard techniques, using a modified peripheral loading pattern, were studied. A postimplant computed tomography (CT) scan was obtained 2-4 h after the implant. The contoured images and sources were entered into a Varian Variseed 7.0 treatment planning system. Dosimetric parameters analyzed included the percent of the postimplant prostate or rectal volume covered by the prescription dose (V100), and the dose that covers 90% of the postimplant prostate volume (D90). Isodose patterns were analyzed at midprostate, and for the entire prostate. Adverse isodose patterns were defined as gaps, holes, islands. Isodose gaps are subprescription intervals between the prostatic margin and the prescription isodose. Isodose holes are regions of subprescription dose within the prostate. Isodose islands are isolated regions > or =prescription dose inside the prostatic margins. RESULTS: Characteristic isodose patterns were predictive for V100 values. Midprostatic isodose holes were seen in 55% of patients with a V100 < 80%, 5% of patients with a V100 of 80-90%, and only 1% of patients with a V100 > 90%. When analyzing the entire prostate, isodose holes were seen in 55% of patients with a V100 < 80%, 18% of patients with a V100 of 80-90%, and 9% of patients with a V100 > 90%. Midprostatic isodose islands were seen in 55% of patients with a V100 < 80%, 5% of patients with a V100 of 80-90%, and no patient with a V100 > 90%. When analyzing the entire prostate, isodose islands were seen in all patients with V100 < 80%, 36% of patients with a V100 of 80-90%, and only 1% of patients with a V100 > 90%. The likelihood of a V100 less than 80% was best predicted by the presence of isodose holes or islands at midprostate. Patients with either finding had an 86% chance of having a V100 < 80%. CONCLUSIONS: These semiquantitative findings can provide practical guidelines for intraoperative dosimetry, to provide a more rational guide to intraoperative postimplant assessment and modification. If isodose holes or islands are seen within the implanted volume, additional seeds are added to the affected region to obtain a V100 > 80%.

Brachytherapy↗
PubMed2003

The effect of supplemental beam radiation on prostate brachytherapy-related morbidity: morbidity outcomes from two prospective randomized multicenter trials.

PURPOSE: To detail the effect of supplemental beam radiation on prostate brachytherapy-related morbidity. METHODS AND MATERIALS: The 220 patients reported here were a subgroup randomized on two treatment protocols, with a planned total accrual of 1200. Low-risk patients, with Gleason Grade 2-6, prostate-specific antigen (PSA) 4-10 ng/mL, were randomized to implantation with I-125 (144 Gy, TG-43) vs. Pd-103 (125 Gy, NIST-99). Intermediate-risk patients, with Gleason Grade 7 or higher or PSA of 10-20 ng/mL, were randomized to implantation with Pd-103, delivering 90 vs. 115 Gy (NIST-1999), with 44 vs. 20 Gy external beam irradiation (EBRT), 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). Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urologic Association (AUA) and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12 and 24 months. Use of alpha-blockers to relieve obstructive symptoms was not controlled for, but was noted at each follow-up time. RESULTS: AUA score increases were highest at 1 month in the patients treated with higher prescription doses of Pd-103 (125 Gy Pd-103 alone or 115 Gy Pd-103 with 20 Gy EBRT), consistent with prior reports. By 6 months, most Pd-103 patients had returned to baseline, whereas I-125 patient scores were still declining. Patients treated with lower dose Pd-103 combined with EBRT had lesser elevations of their AUA scores at 1 and 6 months, but differences between those receiving 20 vs. 44 Gy beam radiation were inconsistent. At no point did beam radiation significantly affect postimplant AUA scores or urinary morbidity scores. Rectal morbidity scores were remarkably similar between groups, apart from higher scores at 1 month in patients treated with full dose Pd-103. Rectal morbidity consisted primarily of increased frequency and mucous passage. There have been no instances of rectal ulceration or fistula. The addition of beam radiation significantly increased postimplant rectal morbidity scores only at the 1-month time point. CONCLUSION: The addition of supplemental beam radiation had little effect on morbidity. We do not believe that morbidity per se should influence the decision of whether or not to use supplemental beam radiation.

Adenocarcinoma↗
PubMed2003

Gross hematuria after prostate brachytherapy.

OBJECTIVES: To summarize the clinical course of postimplant gross hematuria occurring past the perioperative period. METHODS: From 1998 to 2000, 226 patients were treated for prostate carcinoma by implant alone or implant with supplemental external beam radiotherapy, using palladium-103 or iodine-125. Of these 226 patients, 9 had incomplete follow-up information and 2 died of causes other than prostate cancer. As a part of their routine follow-up, the remaining 215 patients were regularly mailed self-reporting questionnaires regarding urinary incontinence and hematuria. Postimplant computed tomography-based dosimetry was available for 211 (98%) of 215 patients. Dosimetric parameters were recorded for each patient using standardized methods. The rates of hematuria resolution were calculated using the product-limit (Kaplan-Meier) method. Statistical significance was determined using unpaired t testing. RESULTS: Twenty-seven patients (13%) reported at least one episode of gross hematuria occurring more than 1 week after prostate implantation. The onset and duration of bleeding varied widely. Eleven patients reported only a single, isolated episode, and 16 patients reported multiple episodes, ranging from isolated sporadic to multiple times per day. No patient required a blood transfusion. The median time from the first episode of hematuria to resolution was 3 months. Of the 27 patients who reported hematuria, 88% had resolved by 24 months from time of first bleeding. Hematuria was unrelated to the maximal or mean urethral dose. CONCLUSIONS: Gross hematuria after brachytherapy resolves spontaneously in nearly all patients. Nonetheless, in patients without a recent workup for a genitourinary malignancy other than prostate cancer, a hematuria workup is reasonable. Because of the retrospective nature of this study and the highly variable presentation and clinical course of postimplant gross hematuria, we are unable to make firmer conclusions or recommendations regarding the role of follow-up urinalysis, urine cytology, anticoagulant medication, or supplemental beam radiation. Such an analysis will require a more controlled, prospective study of a large implant patient population.

Adenocarcinoma↗
PubMed2003

Clinical correlates to PSA spikes and positive repeat biopsies after prostate brachytherapy.

OBJECTIVES: To make some preliminary observations regarding the biochemical characteristics of the doubly confusing picture of prostate-specific antigen (PSA) spikes and histologically positive biopsies after prostate brachytherapy. METHODS: All patients reported here had a pretreatment PSA level of less than 10 ng/mL and Gleason score of 4 to 6. Transperineal iodine-125 implants (without supplemental beam radiotherapy) were performed as previously described. After implantation, patients were followed up routinely, with repeat PSA measurements and physical examinations every 4 to 6 months. The timing of the postimplant PSA measurements was at the discretion of the patients and their doctors. No patient received preimplant or postimplant hormonal therapy. Repeat biopsies were performed from 13 to 31 months (median 22) after implant. RESULTS: Patients' prespike nadir ranged from 0.9 to 1.7 ng/mL (median 1.2). The time from the implant to the start of the spike ranged from 9 to 24 months (median 13). The time from implant to the spike peak ranged from 12 to 30 months (median 22). The peak spike height ranged from 2.6 to 8.4 ng/mL (median 3.1). Patients' last PSA value ranged from 0.1 to 0.5 ng/mL (median 0.2). CONCLUSIONS: Transient PSA rises can occur even in the presence of a persistently positive biopsy, and patients and physicians should not feel compelled to rush ahead with salvage therapy. On the basis of the patient data reported here, it appears that a spike up to 10 ng/mL is still consistent with cancer eradication.

Adenocarcinoma↗
PubMed2003

Morbidity effect of the time gap between supplemental beam radiation and Pd-103 prostate brachytherapy.

PURPOSE: To determine if gap time variations between prostate brachytherapy and supplemental beam radiation (EBRT) affect postimplant morbidity. MATERIALS AND METHODS: Ninety-one patients with 1997 AJC clinical stage T1c-T2a prostatic carcinoma, Gleason grade 7-9, or PSA 10-20 ng/ml, were randomized to implantation with 90 Gy Pd-103 versus 115 Gy (NIST-1999) with 44 Gy versus 20 Gy preimplant supplemental beam radiation, respectively. Pd-103 implantation was performed by standard techniques, using a modified peripheral loading pattern. 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. A post-implant computed tomography (CT) scan was obtained on the same day. Dosimetric parameters analyzed included the V100 - the percent of the postimplant prostate or rectal volume covered by the prescription dose, and the D90 - the dose that covers 90% of the post-implant prostate or rectal volume. For EBRT rectal D90s, the rectal volume included slices 0.9 cm above and below the seminal vesicles and apex, respectively. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urologic Association (AUA) and Radiation Therapy Oncology Group (RTOG) criteria at 1, 3, 6, 12, 18, and 24 months. Use of alpha-blockers to relieve obstructive symptoms was not controlled for, but was noted at each follow-up point. Median follow-up at the time of this analysis was 21 months, with a range of 18-26 months. RESULTS: Variability in the total radiation delivery time within each treatment arm was due almost exclusively to gap time variability. Patients receiving 20 Gy EBRT completed their beam radiation over an average of 12 days (+/-1 day). Patients receiving 44 Gy did so over an average of 31 days (+/- 2 days). The median gap interval for patients receiving 20 Gy EBRT was 5 days (range: 1-40 days) versus 9 days (range: 0-15 days) for patients receiving 44 Gy EBRT. Urinary morbidity, measured by a change in the AUA score from baseline (DeltaAUA) was greater at 1-month postimplant in patients who had shorter gap intervals. The effect of gap time on AUA score changes was lost by 6 months. When looking at the treatment arms separately, the dependence on gap interval was limited to those patients receiving 44 Gy beam radiation. No patient has developed RTOG grade 3 rectal morbidity, and no patient has required invasive therapy for rectal bleeding. There was no relationship between gap interval and rectal morbidity at any time point. There was no relationship between beam doses and RTOG rectal morbidity scores. CONCLUSIONS: The findings reported here are suggestive that short gap times are safe.

Brachytherapy↗
PubMed2003

Prostate brachytherapy seed identification on post-implant TRUS images.

TRUS is a conceptually appealing alternative to CT-based dosimetry, offering the substantial practical advantage of being readily available intraoperatively. To test the feasibility and reliability of seed identification on post-implant TRUS using standard two-dimensional images, ten patients treated with I-125 or Pd-103 brachytherapy were studied. A set of transverse images (6 MHz) were taken immediately following completion of the implant procedure. Original thermal images were sent to four physicians and the sources were identified independently by placing marks on a cellophane overlay, with grids to match the axial TRUS images. The number and type of seed implanted were not revealed to the investigators. Instead, they were instructed to mark the positions of what they would consider, with reasonable certainty, to be seeds. The overlays were then manually compared for source identification and agreement between observers regarding each alleged source. The actual number of implanted seeds ranged from 44 to 108 (median: 60). In contrast, the mean number of seeds allegedly identified per patients ranged from 26 to 82 (median: 43). The average percent of the seeds allegedly identified per patient ranged from 51% to 83% (mean: 74%). The four physician investigators--KW, JS, BH, and GM--identified an alleged median of 90%, 44%, 63%, and 91% of the total seeds, respectively. There were five instances in which investigators alleged more seeds than were actually implanted. The consistency of seed identification among the investigators was evaluated by noting how many investigators identified each bright spot on the images. The percent of bright spots identified by all four investigators ranged from 8% to 33% (median: 20%). Despite considerable interest among some of our clinical and commercial colleagues in developing TRUS-based intraoperative post-implant dosimetry, the use of TRUS-based seed identification for post-implant dosimetry should be viewed with skepticism.

Brachytherapy↗