bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in patients with hormone-refractory metastatic prostate cancer
Authors: Heath E. I. , Hillman D. , Vaishampayan U. , Sheng S. , Sarkar F. H. , Gaskins M. , Pitot H. C. , Tan W. , Ivy P. , Pili R. 
Published: March 2020

15553 Background: 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with anti- proliferative activity in several mouse xenograft models including prostate cancer models. Serum IL-6, IL-8, and maspin are potentially important markers of prostate cancer biology. Methods: Patients (pts) with metastatic, hormone-refractory prostate cancer progressing on at least one prior systemic therapy with rising PSA were eligible. All pts received 17-AAG at a dose of 300 mg/m2 IV weekly for three out of four weeks. Primary objective was to assess the PSA response (50% decrease in PSA). Secondary objectives included Adverse Events (AEs) and correlative serum markers including IL-6, IL-8 and maspin levels. A Simon two-stage design required a total of 25 pts with early termination if < 2 responses occurred among the 1st 16 eligible patients. Results: Seventeen pts were enrolled of which 15 were deemed eligible. Median age was 68 and median PSA was 252 ng/mL. Pts received 17-AAG for a median number of 2 cycles. No pt had a PSA response. No grade 4/5 AEs occurred. Grade 3 AEs included fatigue (4 pts), lymphopenia (2 pts) and back pain (2 pts). The median PSA progression free survival was 1.8 months (95% CI: 1.3–3.4 months). The six-month overall survival was 61% (95% CI: 37%-100%). Due to the lack of PSA response, accrual was stopped per study design. At day 15, the median IL-6 and IL-8 increase from baseline was 0.4 pg/ml (p=0.57) and 3 pg/ml (p=0.73), respectively. Maspin levels had day 15 increase of 6-fold (p=0.44). At treatment failure (TF), the median IL-6 increase from baseline was 4.47 pg/ml (p=0.03) and IL-8 decrease was 1.8 pg/ml (p=0.31). Maspin levels had a 29-fold increase at TF (p=0.09). Conclusions: 17-AAG did not show any activity with regards to PSA response. Serum IL-6 was significantly increased at the time of TF. Further evaluation of 17-AAG at a dose of 300 mg/m2 IV weekly in this patient population is not warranted. No significant financial relationships to disclose.
Titration of dosage of the protective effect of zoledronic acid in patients submitted to androgen-deprivation therapy due to CaP
Authors: Rodrigues P. , Hering F. , Bruna P. , Meler A. E. 
Published: March 2020

15561 Background: Androgen-deprivation therapy is gold-standard treatment for advanced CaP. Zoledronic acid has become a new adjuvant drug for osteoporosis prevention and pain control in patients submitted to androgen-deprivation therapy but regimen of administration is not consensual. Many off-label regimens are used on different occasions. Methods: 64 patients (mean age: 71.7 y-o) after being diagnosed with non-intended to cure therapy were initiated with androgen-deprivation with LHRH agonists at the same time they initiated no treatment (control-16 cases) or monthly (12), bi- monhtly (10), tri-monthly (14) or semestral (12) zoledronic acid infusions for 24 months. Lumbar BMD were evaluated periodically with dual- energy X-ray absorptiometry with densitometry in L2-L4 at 6-month intervals. Tuckey-Kramer and Scheffe`s tests were used for statistical significance of 0.05. Results: Control patients revealed a subgroup showing progressive diminishing BMD along the studied period while another sub-group remained stable. Patients receiving treatment with zoledronic acid showed increasing BMD at the lumbar area (p <0.05) for the 4 treated groups. The protective effects of lumbar BMD were remarkable starting at 18 months in the 4 treated groups with progressive increase of BMD with no clear advantage to any particular regimen (p >0.05). Bone protection could be achieved in the 4 treated groups with no differences for the monthly, bimestral, trimestral or semestral infusions. Conclusions: Zoledronic acid is effective in decreasing bone loss after androgen-deprivation therapy compared to no treatment for osteoporosis. Titration of the dosage regimen of the infusions showed no statistical advantage for any temporal regimen. Reasons for that can only be speculative at this time. [Table: see text] No significant financial relationships to disclose.
Minimal invasive perineal radical prostatectomy
Authors: Albers P. , Schaefers S. , Löhmer H. , De Geeter P. 
Published: March 2020

15566 Background: Radical perineal prostatectomy (RPP) has experienced a reappraisal as excellent surgical treatment option for patients with localized prostate cancer which is competing well with the retropubic (RRP), endoscopic and robotic approaches. Herein we report a new and improved minimal invasive technique of an intrafascial, nerve-sparing and seminal vesical sparing RPP. Methods: From July 2003 to July 2006, 507 radical prostatectomies (317 RPP, 190 RRP) have been performed by 3 surgeons. RPP selection criteria: PSA ≤ 10 ng/ml, Gleason sum ≤ 7, volume ≤ 50 ml. A minimal invasive technique (MI-RPP) was used in 146 of 317 RPP (46%) in order to potentially improve on the results of classical RPP. “Minimal invasive” was defined as an approach with reduced mobilisation of the rectum, intended bilateral nerve-sparing with intrafascial preparation and leaving the seminal vesicals in situ. This approach was compared to classical RPP and to RRP. Perioperative and follow-up data using validated questionnaires were centrally registered using an on-line internet-based prostate cancer data bank provided by the Tumorzentrum Berlin. Results: With a median follow-up of 12 months (0–24), the oncological outcome of patients with MI-RPP was not different to RPP or RRP (comparable T-stages). PSA relapse in MI-RPP, RPP, and RRP in pT2R0 was seen in 10.2%, 14.7%, and 9.7% respectively (n.s.). Continence rates (0–1 pad/d) at 4 weeks were 61.7%, 45.0%, and 43.8%, respectively. This improved at 12 months to 96.3%, 85.7%, and 85.6%, respectively (p < 0,023; p < 0,005). MI-RPP, RPP, and RRP showed pT2 in 70.5, 69.6, and 57.3% with R1pT2 in 1.9, 6.7, and 9.2%, resp. Nerve-sparing was performed in 90.4, 62.0, and 57.4% with median OR times of 90, 141, and 163 min. Catheter removal after more than 13 d was seen in 6.6, 13.6, and 33.3%, resp. Conclusions: MI-RPP represents an improved perineal technique regarding intraoperative and postoperative complications maintaining comparable oncological outcome to RPP and RRP. Leaving seminal vesicals in place did not increase PSA relapse rates. Since OR time is significantly less and early recovery is superior, MI-RPP should be the recommended first-line perineal approach to patients with low risk prostate cancer. At the time of the meeting, data of more than 600 patients will be presented. No significant financial relationships to disclose.
Combined treatment image guided-intensity modulated radiotherapy (IG-IMRT) plus high-dose rate brachytherapy (HDR) and hormonotherapy (HT) as treatment for high-risk prostate cancer: Five-year result of a phase II study
Authors: Guix B. , Bartrina J. , Henriquez I. , Serrate R. , Palombo P. , Vendrell J. , Tello J. 
Published: March 2020

15571 Background: To report early and late toxicity and preliminary biochemical outcome in 345 patients with high-risk (Gleason >=7; PSA>20 or T2c-T3) clinically localized prostate cancer treated with combined high-dose-rate brachytherapy and IMRT (IMRT-HDR) to the prostate and seminal vesicles with 24–36 months of hormononal treatment (goserelin+bicalutamide) (HT). Methods: Between 12/1999 and 10/2003, 345 patients with PSA>20, Gleason score>6 and/or T2c-T3 N0 M0 prostate cancer were treated with IG-IMRT followed by HDR implant to the prostate and HT. Patients were randomly assigned to receive HT for 24 (group 1, 172 patients) or 36 months (group 2, 173 patients). Acute and late toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. PSA failure was defined as nadir +2.0 ng/ml. Results: All patients completed treatment. One patient included in the group 1 and none of the group 2 experienced grade 3 rectal toxicity (rectal ulcer). Seven patients in each group (4.0%) developed acute Grade 2 urinary symptoms, and none experienced urinary retention. No patient (0%) developed Grade 4 rectal complications or grade 3 or 4 urinary complications. With a median follow-up of 44 months, the 5-year actuarial PSA relapse-free survival rates for the whole group of patients was 95.7 %. No statistical differences between group 1 and 2 patients were found. Conclusions: High-dose IG-IMRT+HDR and HT was a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly low, compared with what has been observed with high-dose conventional, 3D-conformal or IMRT-only. Short-term PSA control rates seem to be at least comparable to those achieved with 3D-EBRT or IMRT. Both treatment regimes were very effective. Longer follow-up is needed to know if better PSA control rate are achieved with longer HT. No significant financial relationships to disclose.
Do patients with larger prostates have greater toxicity after external beam radiotherapy for localized prostate cancer?
Authors: Pinkawa M. , Fischedick K. , Asadpour B. , Piroth M. D. , Gagel B. , Krenkel B. , Klotz J. , Eble M. J. 
Published: March 2020

15577 Background: To aim of the study was to assess the impact of prostate volume (PV) on health-related quality of life (HRQOL) before and at different points in time after conformal radiotherapy for prostate cancer. Methods: A group of 180 patients has been surveyed prospectively before (time A), at the last day (B), two months after (C) and sixteen months (median) after (D) radiotherapy (70.2- 72Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Patients in this analysis (n=165) met the prerequisite of responding to the first and last questionnaire. The multi-item scale scores were transformed lineary to a 0–100 scale, with higher scores representing better HRQOL. The group has been divided into a subgroup with a small PV (median 32cc; range 11–45; 83 patients) and a subgroup with a large PV (median 59cc; range 46–151; 82 patients). Results: Treatment plans for large prostates implied a larger planning target volume (averagely 396 vs. 305cc; p<0.01) with a significantly larger dose to the bladder and rectum at all volume levels. Patients with large prostates presented with lower urinary bother (averagely 76 vs. 83; p=0.04), but higher bowel bother scores (averagely 95 vs. 90; p<0.01) before the beginning of treatment. At time B, urinary bother scores decreased stronger for patients with large prostates (averagely 22 vs. 16 points). Comparing posttreatment scores to baseline scores, no significant decrease resulted for urinary function or bother scores for both groups at time C and D. At time D, urinary function scores even increased significantly for patients with large prostates (averagely 4 points). Bowel function and bother scores were still significantly lower for both groups at time C and D (averagely 3–8 points). HRQOL scores did not differ significantly between both patient groups at time D. Conclusions: In spite of a higher dose-load to the organs at risk, lower urinary bother scores before treatment and a higher decrease of urinary scores at the end of radiotherapy for patients with larger prostates, long-term HRQOL scores did not differ significantly between patients with large and small prostates. An improvement of urinary function suggests a regression of hyperplastic prostatic tissue. No significant financial relationships to disclose.
The impact of primary Gleason pattern on survival following brachytherapy for Gleason score 7 prostate cancer
Authors: Adamovich E. , Merrick G. S. , Galbreath R. , Butler W. , Wallner K. , Allen Z. , Gutman S. 
Published: March 2020

15588 Background: A recent radical prostatectomy series reported lower rates of biochemical control and cause-specific survival in Gleason score 7 patients with primary Gleason pattern 4. In this study, we evaluated the impact of Gleason 4+3 versus 3+4 on cause-specific, biochemical progression-free and overall survival in patients managed with permanent prostate brachytherapy. Methods: From April 1995 to June 2003, 530 prostate cancer patients underwent brachytherapy for clinical stage T1b-T3c (2002 AJCC) prostate cancer with Gleason score 3+4 (n=300) or Gleason score 4+3 (n=230) histology. All patients underwent brachytherapy more than three years prior to analysis. The mean and median follow-up was 6.0 and 5.7 years, respectively (range 3.2–11.2 years). Of the evaluated cohort, 412 (77.7%) received supplemental XRT and 177 (33.4%) received androgen deprivation therapy. No statistical differences were discerned between the use of XRT, however, Gleason 4+3 patients were more likely (37.4% versus 30.3%, p=0.002) to receive ADT. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free and overall survival. Results: At 10 years, primary Gleason 3+4 versus 4+3 did not predict for cause-specific survival (96.7% versus 93.3%, p=0.506), biochemical progression-free (97.0 versus 92.9%, p=0.085) or overall survival (77.0% versus 78.0%, p=0.9333). Cox linear regression analysis demonstrated no significant predictors for cause-specific survival while pre-treatment PSA, prostate volume and clinical stage predicted for biochemical progression-free survival. Patient age, tobacco use and diabetes were the strongest predictor for overall survival. To date, 57 patients have died (25 with Gleason 4+3 and 32 with Gleason 3+4). Of the deaths, 76% were due to cardiovascular events or second malignancies. To date, 4 patients (2 in each cohort) have died of metastatic prostate cancer. Conclusions: Following brachytherapy, the primary Gleason pattern did not impact cause-specific, biochemical progression-free or overall survival in Gleason score 7 prostate cancer. Cardiovascular disease and second malignancies were responsible for 9 times more deaths than prostate cancer. No significant financial relationships to disclose.
The effect of androgen deprivation on mini-mental status examination in patients with biochemical recurrence of prostate cancer
Authors: Tan W. , Wehle M. , Graff-Radfford N. , Buskirk S. 
Published: March 2020

15592 Background: Androgen deprivation (AD) is a common treatment option for asymptomatic patients with biochemical recurrence of prostate cancer. Side effects such as sexual dysfunction, hot flashes, fatigue and gynecosmastia have been well documented. However, some of the side effects such as osteoporosis, insulin resistance, hyperglycemia, and anemia have only been recently recognized. The effects of AD on memory are not known. Aim: To determine if there is a decline in cognitive function(CF) in patients on AD using the modified MiniMental Status examination (MMSE). This test was chosen because it was simple, easy to administer and reproducible. Methods: We prospectively enrolled men with biochemical recurrence of prostate cancer prior to initiation of AD and monitored their MMSE at baseline, 2 ,and 4 months and while on AD (Mayo Clinic Jacksonville 8/2004- 9/2006). Results: 38 men were enrolled,however, only 20 men had at least 3 MMSE testing done. (5 withdrew consent, 13 had missing MMSE or lost to followup). The mean age was 68 years, mean baseline MMSE score was 27 and none had a clinical diagnosis of dementia or depression. Comparing the first MMSE and the 2nd MMSE score 19/20 patients had no decline of CF except for one patient who had a transient decline of 5 points in his MMSE score during a period of depression ,however, he had subsequent recovery of his score back to his normal baseline 27. Comparing the first and third MMSE score 20/20 patients had no decline of CF. The mean score change in MMSE score was -1 in 3 patients, 0 in 9 patients, +1 in 4 patients, +2 in 2 patients and +3 in 2 patients. There was no decline of 3 or more points in the mean score in any patient. Interestingly, 2 patients had an 3 point improvement of their MMSE score. We felt that it was secondary to being more familiar to the test process and not due to AD. Conclusions: There is no significant decline in MMSE score in men on AD at 2 and 4 months. MMSE might not be able to detect subtle changes in memory therefore, further study with more sensitive test to discriminate CF decline would be warranted and with longer followup cognitive impairement may be more evident. No significant financial relationships to disclose.
Side effects of sunitinib malate (SM) treatment for patients (pts) with metastatic renal cell carcinoma (mRCC)
Authors: Cartenì G. G. , Montano M. , Perrotta E. , Otero M. , Guida T. , Ragone G. , Aurilio G. , Maiorino L. , Stavolo C. , Panza N. 
Published: March 2020

15617 Background: SM is a tyrosine kinase inhibitor recently approved for treatment of mRCC. Side effects of treatment have been investigated in 51 pts with mRCC and 35 out 51 enrolled pts resulted evaluable for response. Methods: Pts were clinically evaluated before therapy and each month during SM treatment; haematological and biochemical parameters were measured after each cycle. Thyroid function was also evaluated measuring thyroid-stimulating-hormone (TSH), serum free thyroxine (FT4) and triiodothyronine (FT3), before the start and after 6 months of treatment. Results: Toxicity was evaluated according to NCI-CTC. Neutropenia grade 3 was observed in 7 pts (13,7%), grade 2 in 13 (25%); anemia grade 3 was found in 3 pts (5,8%) and grade 2 in 6 (11,7%); thrombocytopenia grade 3 was found in 6 pts (11,7%), grade 2 in 5 (9,8%). Mucositis resulted a frequent side effect. In fact, 4 (7,8%) pts showed a grade 3 toxicity, 16 (31,3%) grade 2 and 10 (19,8%) grade 1 Among 29 out 35 (82,8%) pts who responded to therapy, 3 had mucositis grade 3, 15 grade 2, 9 grade 1. Conversely, among 6 out 35 (17,1%) pts who had progressive disease during treatment, mucositis was observed in only 2 pts. 24 pts out 35 who received 6 months SM treatment were reevalueted for thyroid function. No patient had thyroid dysfunction before treatment. Conversely, 8 pts showed severe ipothyroidism (TSH, FT3 and FT4 out of the normal range) and 6 others intermediate ipothyroidism (only TSH increased over 20 μU/ml) after at least 6 cycles of therapy. Conclusions: SM therapy represents a new interesting approach to the treatment of mRCC, but shows noteworthy side effects. Regular monitoring of thyroid function with administration of levothyroxin substitutive treatment at the appearance of the thyroid disfunction is required. A direct correlation between grade 2–3 mucositis and clinical response to treatment could be postulated on the basis of our data, although a statistical analysis on a greater cohort of subjects is required to confirm this observation. No significant financial relationships to disclose.
Clinical activity of transdermal estradiol in patients with hormone and chemotherapy refractory prostate cancer
Authors: Chhabra S. , Doyle-Lindrud S. , Jeyamohan C. , Metzger D. , Todd M. B. , DiPaola R. S. , Goodin S. , Stein M. N. 
Published: March 2020

15619 Background: Oral estrogens are an effective treatment for metastatic hormone refractory prostate cancer but are not used because of an increased cardiovascular risk, particularly thromboembolism. Use of alternative formulations that bypass first pass metabolism may be safer and more effective. Therefore, we evaluated the anticancer safety and efficacy of transdermal estradiol (TDE) in patients with hormone refractory prostate cancer. Methods: Patients with metastatic prostate cancer who had progressed on hormonal therapy and at least one chemotherapy regimen that included docetaxel (median of 2 prior regimens, range 1–5) were treated with four TDE 0.1 mg/24 hour patches which were changed every 7 days until disease progression or unacceptable toxicity occurred. Serum prostate- specific antigen (PSA) levels were followed at regular intervals. End-points included PSA response, measurable disease response, time-to- progression (TTP), toxicity and quality of life. Results: In this ongoing trial, two patients out of eleven had a PSA response (confirmed PSA decline by = 50%). In five of the nine patients who did not have a ≥ 50% biochemical response to therapy, the PSA level declined between 2.1% and 25.4%, with a median of 19.9%. Two of the eleven patients have continued on study and are on week 9 and week 14, respectively. For the remaining nine patients who are now of study, the TTP ranged from 4 to 19 weeks, with a median duration of 8 weeks. Treatment toxicity included grade 1 nausea, breast enlargement/ tenderness and/or leg edema in six patients. No thromboembolic or cardiovascular events occurred. Conclusions: Early analysis of this ongoing study reveals modest antitumor activity of TDE with minimal toxicity in heavily pretreated patients with hormone refractory prostate cancer. No significant financial relationships to disclose.
Statin use and inflammation in prostate biopsy tissue
Authors: Shannon J. , Collins L. , Adams G. , Luhr G. , Garzotto M. 
Published: March 2020

15624 Background: The statin class of drugs has been shown to affect tumors through a number of mechanisms including inhibiting tissue inflammation. Inflammation is a common finding in men undergoing a prostate biopsy and may play a role in prostatic tumorigenesis. We set out to determine whether the use of statin drugs was associated with altered tissue inflammation on prostate biopsy. Methods: Data were collected on all men with a PSA </= 10 ng/ml that underwent a prostate biopsy. A urinalysis to rule out the presence of infection was carried out in all men. The presence or absence of cancer and/or inflammation was determined by pathology report review. Statin data were recorded from the VA electronic pharmacy database. Statin duration and intensity variables were calculated for each subject based on total days used for each statin at each prescribed dose. Only men with a negative biopsy were considered in our analyses. Odds ratios (OR) as estimates of the relative risk for prostate inflammation associated with each level of statin use and 95 percent confidence intervals (CI) were obtained using pooled conditional logistic regression stratified on year of biopsy. Results: Out of 1,482 men with data available on inflammation, family history of prostate cancer, age and race; 436 were found to have prostatic inflammation. In final adjusted models stratified on year of biopsy (prior to 1997, 1997–2001, 2001 -2006) we found no association between any statin use (OR=0.88, 95% CI (0.70–1.11)), intensity of use (OR=0.93, 95% CI (0.86–1.01)), or duration of use (OR=0.932, 95% CI (0.86–1.01). These results did not change when individual statin types were analyzed. Conclusions: Statin use was not associated with a reduction in tissue inflammation in men undergoing a prostate biopsy. If statin use affects prostatic carcinogenesis, it is unlikely to do so by affecting tissue inflammatory networks. No significant financial relationships to disclose.