Biomedical subjects

R G Stock

Publications and source records attributed to R G Stock.

At least 37 records · Page 2Linked to original sources

PubMed2000

Use of radioimmunoscintigraphy with indium-111-labeled CYT-356 (ProstaScint) scan for evaluation of patients for salvage brachytherapy.

PURPOSE: Indium 111 capromab pendetide radioimmunoscintigraphy (ProstaScint) has been used to detect occult recurrent carcinoma after radical prostatectomy. MATERIALS AND METHODS: We evaluated the role of ProstaScint in 24 men with rising prostate-specific antigen (PSA) level following definitive radiation therapy to differentiate between local and distant recurrence in this patient population. RESULTS: ProstaScint scan detected prostatic uptake only in 16 patients, extraprostatic uptake in 5, both prostatic and extraprostatic uptake in 1, and no uptake in 2. Ten of 21 patients with prostatic uptake had positive biopsies, 5 had negative biopsies, and 6 were not biopsied. Two of the three patients with negative scans had positive biopsies, and the third patient was not biopsied. Three patients had evidence of osseous metastasis on radionuclide bone scan, two corresponding to the sites detected on ProstaScint. All three patients had abnormal uptake beyond the prostatic fossa with (n =2) or without (n = 1) prostatic uptake. There were no positive bone scans in patients without extraprostatic uptake on ProstaScint. CONCLUSIONS: ProstaScint scan is useful in detecting occult recurrence outside the prostate in patients with rising PSA following radiation therapy. Compared to data from radical prostatectomy, ProstaScint scans in these patients reveal a higher prevalence of abnormal uptake in the prostate and less frequent extraprostatic uptake.

Aged↗

PubMed2000

Effects of neoadjuvant hormonal therapy on prostate biopsy results after (125)I and (103)Pd seed implantation.

BACKGROUND: Androgen ablation may improve the efficacy of radiation therapy. PATIENTS AND METHODS: A total of 296 patients who had either (125)I (206; 70%) or (103)Pd (90; 30%) transperineal prostate brachytherapy (no external-beam radiation) had routine transrectal ultrasound-guided needle biopsy (minimum six cores) 2 years after treatment without regard to disease status. Neoadjuvant hormonal therapy (NHT: leuprolide acetate and flutamide) was used in 115 patients (39%) for 3 months prior to and 3 months after the implant. RESULTS: Of the 296 patients, 30 (10%) had positive prostate biopsies. Biopsies were positive in 4 of 115 (3.5%) v 26 of 181 (14%) of those who received or had not received NHT, respectively (P = 0.002). When patients were separated into low risk (PSA < or = 10 ng/mL, stage < or = T(2a), and Gleason score < or = 6) and high risk (all others), it was seen that low-risk patients did not benefit from NHT (3.8 v 7.7% positive biopsy rate; P = 0.5) whereas high-risk patients did (3.4% v 21.1%; P = 0.003). CONCLUSION: Prostate brachytherapy yields high negative biopsy rates (90%) 2 years after treatment. Neoadjuvant hormonal therapy can improve the local control rates (as determined by biopsy) in patients undergoing (125)I or (103)Pd seed implantation. These results are most significant for patients who present with PSA >10 ng/mL, stage > or = T(2b) diseases, or Gleason score > or = 7 (high-risk status).

Androgen Antagonists↗

PubMed1999

Does prostate brachytherapy treat the seminal vesicles? A dose-volume histogram analysis of seminal vesicles in patients undergoing combined PD-103 prostate implantation and external beam irradiation.

PURPOSE: Combined brachytherapy of the prostate and external beam irradiation (EBRT) of the prostate and seminal vesicles (SV) is becoming a popular treatment for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV in patients undergoing this treatment was performed to determine the dose distribution to the SV and the adequacy of this treatment in patients with potential SV involvement. METHODS AND MATERIALS: Twenty-five consecutive patients were treated with a Pd-103 implant of the prostate alone and 45 Gy of EBRT to the prostate and SV. Attempts were not made to implant the SV but seeds were routinely placed at the junction of the prostate and SV. All patients underwent CT-based postimplant dosimetric analysis 1 month after implantation. As part of this analysis, DVH were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 6-mm-thick volumes identified as SV1, SV2, SV3, SV4, and SV5 starting from the junction of the prostate and SV and extending distally. DVH were also generated for these structures. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). RESULTS: The median volumes in cc of the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 34.33, 9.75, 2.7, 3.48, 2.92, 3.18, and 1.96 respectively. The SVT contained from 0-9 seeds (median 2). There was little dose delivered to the SVT and SV volumes from the implanted prostate. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 8615 cGy, 675 cGy, 3100 cGy, 1329 cGy, 553 cGy, 246 cGy, and 67 cGy, respectively. The dose delivered to the prostate covered small percentages of SV. The percents of SV volumes covered by the prostate D90 were 11, 35, 3.3, 0, 0, and 0 for SVT, SV1, SV2, SV3, SV4, and SV5, respectively. CONCLUSIONS: DVH analysis of the SV reveals that dose generated from an implanted prostate contributes little to the SV. Those patients at high risk for SV involvement may be undertreated with combined EBRT to prophylactic doses and prostate implantation.

Brachytherapy↗

PubMed1999

Rectal cancer and inflammatory bowel disease: natural history and implications for radiation therapy.

PURPOSE: There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with IBD and rectal cancer in order to determine the natural history of the disease as well as the effect and tolerance of pelvic irradiation. METHODS AND MATERIALS: A retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thirty-five patients had ulcerative colitis and 12 patients had Crohn's disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients, stage III in 13 patients, and stage IV in 9 patients. Surgical resection was performed in 44 patients. In two of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent postoperative adjuvant therapy (12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 patient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months). RESULTS: The 5-year actuarial results revealed an overall survival (OS) of 42%, a disease-free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5-year rate of 86% for patients with Tis-T2 disease compared to 10% for patients with T3-T4 disease (p < 0.0001). The presence of lymph node metastases also resulted in a decrease in DFS with a 5-year rate of 67% for patients with NO disease compared to 0% for patients with N1-N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grade with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respectively (p = 0.03). The T and N stages showed a statistically significant effect on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopathologic grade of the tumor did not significantly affect pelvic control. An analysis of high-risk patients (30) with T3-T4 or N1-N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26%, and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving RT (14 patients) with a 5-year PC of 60% compared to a rate of 23% for those patients not irradiated (16 patients). Acute complications (grade 3 or >) were noted in three patients (20%) receiving pelvic irradiation +/- chemotherapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastrointestinal toxicity. Two patients (13%) developed small bowel obstruction at 2 and 4 months, respectively, postirradiation which were managed conservatively. There were no long-term complications in patients irradiated. CONCLUSION: Treatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patients appeared to have a poorer outcome. In light of this finding and the ability of these patients to tolerate chemotherapy and pelvic irradiation, aggressive adjuvant therapy should be given to IBD-associated rectal cancer patients with high-risk features.

Adolescent↗

PubMed1999

PSA kinetics following I-125 radioactive seed implantation in the treatment of T1-T2 prostate cancer.

Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment.

Adenoma↗

PubMed1999

Prostate brachytherapy: treatment strategies.

PURPOSE: Patients who present with localized and locally advanced prostate cancer may be candidates for prostate brachytherapy. We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low, moderate and high risk features. MATERIALS AND METHODS: A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and/or external beam irradiation. Of these patients 109 at low risk with prostate specific antigen (PSA) 10 ng./ml. or less, Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone, 152 at moderate risk with PSA greater than 10 ng./ml., Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy, and 40 at high risk with PSA greater than 15 ng./ml., Gleason 8 or greater, clinical stage T2c to T3 or positive seminal vesicle biopsy (20) were treated with combination brachytherapy, external beam irradiation and 9 months of hormonal therapy. Patients with a positive seminal vesicle biopsy (T3c disease) and negative pelvic lymph nodes were included in the high risk group, and the walls of the seminal vesicles were also treated with implantation. Followup was performed every 6 months with digital rectal examination and ultrasound evaluation. Prostate biopsy was routinely recommended 2 years after completion of the radiation. Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml. or evidence of local recurrence on digital rectal examination, transrectal ultrasound or biopsy. Kaplan-Meier projections were used to calculate progression-free survival rates. RESULTS: Of the 109 patients at low risk followed from 1 to 7 years (median 18 months) 91% were free of PSA failure at 4 years. No patient experienced urinary incontinence following implantation, although grade 1 to 2 radiation proctitis occurred in 5 (4.5%). Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy. The 4-year biochemical freedom from failure rate for the hormone group was 85% versus 58% for the no hormone group (p = 0.08). The difference was more significant for those with Gleason score 7 or greater (90 versus 43%, p = 0.01) and for those with PSA greater than 10 ng./ml. (87 versus 59%, p = 0.04). Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients (1.3%) receiving hormonal therapy and in 3 (4%) treated with implantation only. There were no cases of urinary incontinence. Of the 40 patients at high risk 71% were free of biochemical failure at 3 years. Of the 4 patients with failure (10%) 3 (75%) originally had positive seminal vesicle biopsies. Five patients experienced gastrointestinal complications, although none was grade 3 or 4. The actuarial freedom from grade 2 proctitis was 82%. No patient experienced urinary incontinence. Prostate biopsies were negative in 87% of the low risk, 96.8 (hormone group) versus 68.6% (no hormone group) of the moderate risk (p = 0.0023) and 86% of the high risk patients. CONCLUSIONS: Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent. Adopting a strategy of implant alone, implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases.

Brachytherapy↗

PubMed1999

Permanent radioactive seed implantation in the treatment of prostate cancer.

Prostate brachytherapy has come a long way in the last 15 years, from an open free-hand technique with which seed placement was often inaccurate to the highly technical and accurate procedure of today. It has become a viable treatment option for low-risk patients along with EBRT and prostatectomy. Its most promising use may be in combination with hormonal therapy and EBRT in moderate- to high-risk patients, for whom it may offer improved outcomes over standard single-modality therapies.

Brachytherapy↗

PubMed1999

Laparoscopic pelvic lymph node dissection in the staging of prostate cancer.

BACKGROUND: Men with localized prostate cancer who present with high risk features may benefit from determination of pelvic lymph node status by a laparoscopic lymph node dissection prior to definitive therapy. METHODS: One hundred eighty-nine men with a median age of 69 years (range 49-80) with T1-T3 prostate cancer had a laparoscopic pelvic lymph node dissection (LPLND) prior to definitive therapy (radiation or surgery). All patients had a negative bone scan and a computerized tomography of the pelvis prior to the LPLND. In addition, all patients also underwent a seminal vesicle biopsy (SVB) in order to determine the presence of T3c disease. Prostate-specific antigen (PSA) ranged from 1.6-190 ng/mL (median 11 ng/mL) and was > 10 ng/mL in 56.6%, Gleason score was > or = 7 in 46.7%, and 67.8% had clinical stage T2b-T3a. RESULTS: Of the 189 patients who underwent an LPLND, 22 (11.6%) had a positive dissection. Between 1 and 51 nodes (median 9) were removed per dissection. PSA, clinical stage, Gleason score and SVB results all significantly influenced node findings. Positive nodes were encountered in 26.5% of those with a PSA > 20 ng/mL (p = 0.0002), in 16.4% with stage T2b-T3a (p = 0.003), in 20% with Gleason scores 7-10 (p = 0.0006) and in 38% of men with a positive SVB (p < 0.0001). Logistic regression analysis with PSA, Gleason score, clinical stage and the results of the SVB demonstrated that a positive SVB was the most significant predictor of node positivity. The overall transfusion rate was 1% (2/189) and median hospital stay was one day. The complication rate for the LPLND was 9% (17/189). CONCLUSION: The LPLND is an effective and efficient means of detecting positive pelvic lymph nodes in patients with localized prostate cancer. It should be considered a necessary diagnostic modality in all appropriate patients who may be candidates for curative therapy.

Aged↗

PubMed1998

A dose-response study for I-125 prostate implants.

PURPOSE: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results. MATERIALS AND METHODS: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant. RESULTS: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29). CONCLUSION: A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.

Brachytherapy↗

PubMed1998

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States.

PURPOSE: To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. METHODS AND MATERIALS: Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. RESULTS: Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. CONCLUSION: While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.

Brachytherapy↗

PubMed1998

A survey of current clinical practice of permanent prostate brachytherapy in the United States.

PURPOSE: To help establish standards of care for transperineal interstitial permanent prostate brachytherapy (TIPPB) by obtaining data regarding current clinical practice among the most experienced TIPPB brachytherapists in the United States. METHODS AND MATERIALS: The 70 brachytherapists who performed the greatest number of TIPPB cases in 1995 in the U.S. were surveyed. Each received a comprehensive four page questionnaire that included sections on training and experience, patient and isotope selection criteria, manpower, technique, and follow-up. Thirty-five (50%) surveys were ultimately returned after three mailings and follow-up phone calls. The cumulative experience of the 35 respondents represented approximately 45% of the total TIPPB volume in the U.S. for 1995. Respondents included 29 from the private sector and six from academic programs. RESULTS: The median physician experience with TIPPB was reported as 4.9 years. Each performed an average of 73 TIPPB procedures in 1995 (range 40-300). This represented an increase in volume for most (74%) of the respondents. Sixty-three percent of the respondents attended a formal training course, 54% had TIPPB-specific residency training, and 31% had been proctored (16 had received two or more types of training experience). The most commonly reported selection criteria for implant alone was on Gleason score < or = 7, PSA < 15, < or = Stage T2a, and gland size < or = 60 cc, although no clear consensus was found. Fifty-four percent considered a history of TURP to be a relative contraindication, while 34% considered TURP to have no impact on patient selection. Eighty-six percent of respondents combine brachytherapy with external beam radiation in an average of 32% of their patients. Boosts were given with both 125I prescribed to 120 Gy (75%) or 103Pd to 90 Gy (50%). Sixty percent reported using a Mick applicator, 46% prefer using preloaded needles, and (11%) use both techniques. Real-time imaging was usually performed with ultrasound (94%); most included fluoroscopy (60%). Definitions of PSA control varied widely. CONCLUSIONS: TIPPB clinical practice in the U.S. demonstrates similarities in technique, but differences in patient selection and definitions of biochemical control. It is, therefore, incumbent on those beginning TIPPB programs to carefully review the specific practice details of those institutions with a broad experience.

Brachytherapy↗

PubMed1998

Acute urinary morbidity following I-125 interstitial implantation of the prostate gland.

The objective of this paper was to evaluate the acute urinary morbidity associated with I-125 interstitial implantation of the prostate gland. From 1991-1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75 Gy). The patients' urinary symptoms were recorded pre-implantation and at regular intervals after implantation using the International Prostate Symptom Score (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms: incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Median follow-up was 12 months. The natural history of implant-related urinary symptoms was assessed in this manner. In addition, dosimetric factors including U/S prostate volume, total activity, activity per seed, dose volume histogram (DVH) values for dose to gland, and dose area histogram (DAH) values for dose to urethra and bladder were examined for correlation to the severity of each symptom as well as to total IPSS (sum of the individual symptom scores). Total IPSS peaked at 1 month post-implant and gradually returned to approximately baseline at 24 months. Total IPSS directly correlated with total activity and DVH for the prostate. Total IPSS, however, did not correlate with bladder or urethral DAH. With the exception of frequency, individual symptoms did not correlate with dose to gland, bladder, or urethra. Frequency scores did, however, correlate not only with dose to prostate gland but also dose to urethra. The acute urinary side effects of I-125 prostate implantation are transient and peak at 1 month post-implant. The severity of the urinary irritative symptoms developed are closely related to total dose to the gland. Urethral dose appears to affect frequency most significantly. Urinary symptoms, therefore, may be a limiting factor when considering dose escalation with I-125.

Acute Disease↗

PubMed1998

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer.

Epidemiological studies have demonstrated a clustering of breast and prostate cancers in some families. Moreover, there is an increase in the number of cases of prostate cancer in families with inherited mutations of the breast cancer susceptibility gene BRCA1. We assessed the role of BRCA1 and BRCA2 in prostate cancer. We tested for the BRCA1 185delAG frameshift mutation, found in 0.9% of Ashkenazi Jews, and the BRCA2 6174delT mutation, found in 1% of Ashkenazi Jews, in Ashkenazi Jewish men with prostate cancer. We studied 60 Ashkenazi men with prostate cancer. A family history was obtained by interview or a self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. Mutations of BRCA1 and BRCA2 were detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Patients' ages ranged from 55 to 80 years (mean +/- s.d. 70 +/- 5.25). There were six men with a family history of prostate cancer; three of these had a father with prostate cancer. Five of the men had a family history of breast cancer, in a mother, a sister or an aunt. None of the men had a family history of both breast and prostate cancer. None of the 60 men carried the 185delAG BRCA1 or 6174delT BRCA2 mutations. Of 268 Ashkenazi Jewish women with sporadic breast cancer, tested in an unrelated study, 16 carried either the 185delAG mutation of BRCA1 or the 6174delT mutation of BRCA2. There was a significant difference in the incidence of the BRCA1 and BRCA2 mutations in the breast and prostate cancer cases (P = 0.05, two-tailed Fisher's exact test). The contribution of germline BRCA1 and BRCA2 mutations to prostate cancer incidence is probably small and could be limited to specific subgroups.

Aged↗

PubMed1998

Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate.

PURPOSE: Urinary retention is a frequently reported complication following radioactive seed implantation of the prostate. If retention is refractory, a post-implant transurethral prostatic resection may ultimately be required to relieve obstruction, leading to an increased risk of urinary incontinence. In this series the incidence of prolonged urinary retention was determined, and the effect of pretreatment and treatment related factors was analyzed to identify high risk patients. MATERIALS AND METHODS: A total of 251 patients with organ confined prostate carcinoma underwent transperineal prostate seed implantation. Of the patients 114 were implanted with 103palladium (103Pd) and 137 with 125iodine seeds. Of the patients who were implanted with 103Pd 90 received 3 months of neoadjuvant hormonal therapy. All patients had International Prostate Symptom Scores (I-PSS) recorded before implantation to assess the degree of urinary symptoms. In the patients receiving neoadjuvant hormones prostate volumes and I-PSS were recorded before initiation of hormone treatment and 3 months later at the time of implant. RESULTS: Urinary retention developed in 14 patients requiring catheterization for more than 48 hours. Median time to onset was 1 day after implant. Of these patients 6 ultimately required transurethral prostatic resection to relieve urinary obstruction. No patient had urinary incontinence following implantation or transurethral prostatic resection. Multivariate analysis revealed that pretreatment I-PSS, and combined treatment with hormonal therapy and 103Pd predicted for the development of retention. Patients with I-PSS 20 or greater had a 29% risk, I-PSS 10 to 19, 11% risk and I-PSS less than 10, 2% risk of retention. Neither patient age, clinical stage, prostate specific antigen, Gleason score, use of 125I nor prostate volume was significant. A subgroup analysis of patients receiving hormonal therapy and 103Pd revealed that those with persistent urinary symptoms (I-PSS 10 or greater) following 3 months of hormonal therapy had the greatest risk of prolonged retention (37%). CONCLUSIONS: The overall risk of prolonged urinary retention following prostate implantation was low in our series. Using the I-PSS questionnaire, high risk patients can be identified before treatment. Patients with significant pretreatment urinary symptoms or persistent urinary symptoms following 3 months of hormonal therapy and then implantation with 103Pd have the greatest risk.

Aged↗

PubMed1998

Perineural invasion and seminal vesicle involvement predict pelvic lymph node metastasis in men with localized carcinoma of the prostate.

PURPOSE: We evaluate the contribution of perineural invasion and seminal vesicle biopsy results in predicting pelvic lymph node metastases in men with T1 or T2 adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 212 men with localized prostate cancer were evaluated for serum prostate specific antigen (PSA), clinical stage, Gleason score and the presence of perineural invasion. Each patient had undergone seminal vesicle biopsies and a laparoscopic pelvic lymph node dissection before definitive therapy. The pretreatment prognostic values, presence of perineural invasion and seminal vesicle involvement were compared to the results of the laparoscopic pelvic lymph node dissection. Differences in proportions were tested using the Pearson chi-square test. The effect of multiple variables was tested using a stepwise logistic regression analysis. RESULTS: PSA ranged from 1.6 to 190 ng./ml. (median 11), and 52% of patients had Gleason score 7 or greater and 67.5% had clinical stage T2b or greater disease. Of the 212 patients 37 (17.5%) had perineural invasion, 43 (20.3%) seminal vesicle involvement and 21 (10%) positive node dissections. A PSA greater than 20 ng./ml. (20 versus 6.8%, p = 0.006), Gleason score 7 or greater (15.5 versus 3.9%, p = 0.005), clinical stage T2b or greater (14 versus 0.6%, p = 0.004), presence of perineural invasion (27 versus 6%, p = 0.0001) and seminal vesicle involvement (32.6 versus 4.1%, p <0.0001) influenced nodal findings. However, in the logistic regression model only the positive seminal vesicle biopsy (p = 0.0006), presence of perineural invasion (p = 0.04) and PSA greater than 20 ng./ml. (p = 0.044) were significant variables. Of the 21 men with positive node dissections 18 (85.7%) had a positive seminal vesicle biopsy or perineural invasion. Separation of patients into a high risk group defined by a positive seminal vesicle biopsy or perineural invasion, or a low risk group defined as the absence of these features yielded a significant association with nodal involvement (28 versus 2%, p <0.0001). A separate analysis of the patients with a negative seminal vesicle biopsy demonstrated that only perineural invasion (19 versus 2%, p = 0.0002) and PSA greater than 20 ng./ml. (12 versus 2%, p = 0.01) conferred a greater risk of nodal metastases. A logistic regression analysis in the negative seminal vesicle biopsy group discarded all of the variables other than perineural invasion as significant. CONCLUSIONS: A positive seminal vesicle biopsy is the most significant predictor of pelvic lymph node metastases in men with T1 or T2 prostate cancer. Perineural invasion is also an independent predictor of nodal disease. Patients with either of these features should undergo pelvic lymph node dissection before receiving definitive therapy.

Adenocarcinoma↗

PubMed1998

Does pelvic irradiation play a role in the management of prostate cancer?

The optimal management of patients with lymph node-positive prostate cancer remains controversial. The role of pelvic irradiation in patients at high risk for nodal involvement continues to be debated. Studies of prostate irradiation with and without inclusion of the pelvic lymph nodes show poor outcomes for node-positive patients, supporting the concept that many of these patients have systemic disease at presentation. Although no randomized trial has examined the role of pelvic irradiation in pathologically node-positive patients, available data fail to reveal any significant benefit of this approach over prostate-alone irradiation. More promising therapeutic approaches involve the combination of local therapy and sustained hormonal therapy. Series comparing prophylactic irradiation of the pelvis and prostate to irradiation of the prostate alone have shown no clear benefit of pelvic irradiation. Pelvic irradiation may play a role in the treatment of early-stage or occult nodal disease, although this has yet to be examined. Until prospective, randomized trials demonstrate the efficacy of pelvic irradiation in the management of prostate cancer, its use cannot be routinely recommended. Data support the use of lymphadenectomy in high-risk patients to identify those with positive nodes, since these patients require androgen withdrawal therapy.

Clinical Trials as Topic↗

PubMed1997

A new technique for performing Syed-Neblett template interstitial implants for gynecologic malignancies using transrectal-ultrasound guidance.

PURPOSE: Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately, the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide needle placement into tumor and avoid needle insertion into critical surrounding normal structures. METHODS AND MATERIALS: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum. Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition, it can be used to assess the length of the target volume and aid in determining the active length of the sources. RESULTS: A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min). CONCLUSION: Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial implantation of gynecologic malignancies and allows for accurate needle placement.

Aged↗

PubMed1997

Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of locally advanced cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma. MATERIALS AND METHODS: Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months). RESULTS: The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment. CONCLUSION: Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.

Antineoplastic Combined Chemotherapy Protocols↗