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Lawrence True

Publications and source records attributed to Lawrence True.

15 recordsLinked to original sources
PubMed2006

A molecular correlate to the Gleason grading system for prostate adenocarcinoma.

Adenocarcinomas of the prostate can be categorized into tumor grades based on the extent to which the cancers histologically resemble normal prostate glands. Because grades are surrogates of intrinsic tumor behavior, characterizing the molecular phenotype of grade is of potential clinical importance. To identify molecular alterations underlying prostate cancer grades, we used microdissection to obtain specific cohorts of cancer cells corresponding to the most common Gleason patterns (patterns 3, 4, and 5) from 29 radical prostatectomy samples. We paired each cancer sample with matched benign lumenal prostate epithelial cells and profiled transcript abundance levels by microarray analysis. We identified an 86-gene model capable of distinguishing low-grade (pattern 3) from high-grade (patterns 4 and 5) cancers. This model performed with 76% accuracy when applied to an independent set of 30 primary prostate carcinomas. Using tissue microarrays comprising >800 prostate samples, we confirmed a significant association between high levels of monoamine oxidase A expression and poorly differentiated cancers by immunohistochemistry. We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17 beta4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively. The altered expression of these genes provides functional insights into grade-associated features of therapy resistance and tissue invasion. Furthermore, in identifying a profile of 86 genes that distinguish high- from low-grade carcinomas, we have generated a set of potential targets for modulating the development and progression of the lethal prostate cancer phenotype.

Adenocarcinoma↗
PubMed2006

Brachytherapy in men aged < or = 54 years with clinically localized prostate cancer.

OBJECTIVE: To report the biochemical progression-free survival (BPFS) in hormone-naive men aged < or = 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non-extirpative approaches for young men with clinically localized prostate cancer. PATIENTS AND METHODS: From April 1995 to October 2002, 108 hormone-naive patients aged < or = 54 years (median 52 years, range 45-54) had permanent interstitial brachytherapy for clinical stage T1c-T2c NXM0 (2002 American Joint Committee on Cancer staging) prostate cancer. No patient had a seminal vesicle biopsy or pathological lymph node staging. The mean (sd, median) follow-up was 5.3 (1.8, 4.8) years. BPFS was defined by a prostate-specific antigen (PSA) level of < or = 0.40 ng/mL after the nadir. Risk groups were assigned using the Memorial Sloan-Kettering Cancer Center criteria. Several clinical, treatment and dosimetric variables were evaluated for their effect on BPFS. RESULTS: For the entire group, the actuarial 8-year BPFS was 96%; for low- (57 men), intermediate- (47) and high- (four) risk patients, the BPFS rates were 96%, 100% and three of four, respectively. For biochemically disease-free patients, the median PSA level after treatment was 0.05 ng/mL. In a multivariate analysis, only pretreatment PSA level predicted biochemical control, while dosimetry variables after treatment were almost statistically significant. CONCLUSIONS: Hormone-naive patients aged < or = 54 years have a high probability of a good 8-year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.

Brachytherapy↗
PubMed2006

Multicolor quantum dots for molecular diagnostics of cancer.

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.

Animals↗
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.

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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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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.

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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

Long-term outcomes after treatment with external beam radiation therapy and palladium 103 for patients with higher risk prostate carcinoma: influence of prostatic acid phosphatase.

BACKGROUND: The objective of this study was to define the long-term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early-stage prostate carcinoma. METHODS: One hundred sixty-one consecutive patients with Stage T1-T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score > or = 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd-103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd-103 dose to the prostate was 80 Gy (pre-National Institute of Standards and Technology [NIST]-99). Freedom from biochemical failure was defined as a serum PSA level < or =0.2 ng/mL at last follow-up. RESULTS: There was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty-eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP (P = 0.0001), followed by Gleason score (P = 0.13), and PSA (P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses. CONCLUSIONS: The biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long-term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice.

Acid Phosphatase↗
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↗
PubMedDate not supplied

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

PURPOSE: The purpose of this study was to test the hypothesis that the shorter half-life of Pd-103 versus I-125 results in a shorter duration of radiation-related symptoms after prostate brachytherapy. METHODS: As of February 2000, 110 of a planned total of 380 patients with 1997 American Joint Commission clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, prostate-specific antigen, 4-10 ng/mL) had been randomly assigned to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. 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 point. All patients reported here have a minimum 1-year follow-up. Randomization was carried out at a central enrollment office where eligibility criteria were confirmed and the patient assigned by computerized random number generator to one of the two treatment arms. Patients were assigned to 95 blocks of four. Most statistical comparisons shown here are by Student's unpaired t-test at specific follow-up times, as indicated in the figure legends. Additionally, considering the patients' scores change overtime, repeated measures were incorporated in a mixed model assuming an unstructured covariance matrix. RESULTS: Patients in each arm were well matched by preimplant prostate volume, AUA score, and age. The AUA scores peaked at the 1-month point for both isotopes and then gradually declined. The difference was greatest at 6 months, when I-125 patients had a mean AUA score of 16 (+/- 8), compared with 11 (+/- 10) for the Pd-103 patients. By 12 months, mean AUA scores for the Pd-103 patients had decreased to 12 (+/- 9), compared with 13 (+/- 8) for the I-125 patients. At 6 months after implantation, 41% of Pd-103 patients were still taking alpha-blockers, versus 44% of I-125 patients. The differences between isotopes were more marked in patients with a low pretreatment AUA score or smaller preimplant transrectal ultrasonography volume. Results of the mixed model, incorporating repeated measures for each patient, showed that the effect of isotope choice on AUA score depended on time. This effect was further dependent on baseline AUA score, but not on transrectal ultrasonography volume or on age. Urinary and rectal morbidity was generally low, typically grade 1 or 2. There was a trend to greater morbidity with I-125 than with Pd-103, most markedly at the 6-month time point. DISCUSSION: Patients treated with Pd-103 recovered from their radiation-induced prostatitis sooner than I-125 patients. It appears that patients with minimal pretreatment urinary obstructive symptoms are the most likely to experience implant-related exacerbations of their symptoms and are the most likely to benefit from the more rapid half-life of Pd-103 rather than I-125.

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PubMedDate not supplied

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↗
PubMedDate not supplied

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↗