bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of late relapse after surveillance for stage I mixed (M) or non seminomatous (NS) testicular germ cell tumors (TGCT)
Authors: Theodore C. , Droupy S. , Laplanche A. , Wibault P. , Fizazi K. , Terrier-Lacombe M. 
Published: March 2020

14576 Background: Surveillance is an alternative to retroperitoneal lymph node dissection or adjuvant chemotherapy for stage I M or NS TGCT. It has been shown to be associated with a low mortality rate of about 1%, similar to that of the other therapeutic options. However, there are few reports of long-term results. The aim of this retrospective study was to investigate late relapses in this setting. Methods: Screening of the computerized database from 1984 to 2005 for patients (pts) treated for a relapse of a M or NS TGCT at 10 years or more after an orchidectomy. Results: From 1994 to 2006, the files of 5 pts were retrieved. Two pts were referred from other institutions whereas 3 pts had initially been included in the surveillance program of the Institution out of a total of 88 from 1984 to 1996. (3.4% CI 95% 0.7–9.6). Initial histology was available in 4pts: it was pure mature and immature teratoma in one pt and mixed GCT with seminoma in 3 pts. There was no vascular invasion in any of the tumors. Relapse occurred between 10 and 13 years after orchidectomy (median 11 years). The diagnosis of relapse was made based on a systematic 10-year follow-up CT scan in one pt. The 4 other pts who relapsed presented with symptoms: abdominal and back pain due to retroperitoneal involvement in 2 pts, walking disability due to a spinal cord compression in one pt and acute respiratory distress syndrome due to massive metastatic lung involvement in one pt respectively. All 4 pts had bulky retroperitoneal masses. According to the IGCCCG classification, the prognosis was poor in 2 pts and intermediate in 2pts. One pt died of disease despite cisplatin-based chemotherapy. Conclusion: These data demonstrate that there is a small but clinically significant risk of late relapse of stage I M or NS GCT after orchidectomy alone and support the need for long-term surveillance and patient information. No significant financial relationships to disclose.
Targeted molecular imaging of prostate cancer using tumor endothelium homing Arg-Arg-Leu peptides
Authors: Henry D. O. , Chen S. C. , Wong M. K. 
Published: March 2020

14582 Background: Tumor endothelial cells express a specific and unique cell surface signature. We have previously reported on the discovery of tumor endothelial cell (TDEC) binding peptides that possess the amino acid sequence Arg-Arg-Leu (RRL). We now show specific binding of this synthetic peptide to both surgically resected and experimental human prostate adenocarcinoma tumors thereby allowing for tumor imaging. Methods and Results: Cryosections from human lung, colon, renal, breast and prostate cancers were immunohistochemically processed to reveal the relationship of RRL-peptide staining in relation to Factor VIII labeled tumor vasculature. The RRL-peptide tightly co-localizes onto tumor endothelium within human prostate adenocarcinomas, and did not stain the tumor cells proper. Alexa 680, 800 are two near-infrared dyes that can be conjugated to RRL peptide and which emit at a wavelength unquenched by biologic tissue, thus permitting whole animal imaging. Intravenous administration of RRL-peptide-Alexa chimera to human PC3 prostate tumor bearing mice or TRAMP (transgenic prostate cancer) mice results in the fluorescent visualization of tumors within the intact animal through the prolonged intra-tumor retention of the RRL-dye complex as compared to controls. Direct time-lapse intravital microscopy of such tumors show real-time tumor vascular binding of the RRL peptide. Whole animal imaging revealed the tumor and did not show an appreciable image signal at any other site or organ. Conclusion: The RRL peptide homes to prostate vasculature and is useful for the specific detection of experimental prostate tumors in vivo. Further development of the RRL-peptide into a drug delivery and imaging agent is underway. No significant financial relationships to disclose.
Miniautologous transplantation of lymphokine-activated killers (LAK) in cytokine-pretreated patients with metastatic renal cell carcinoma (RCC): A Slovak phase II study
Authors: Mardiak J. , Lakota J. , Sycova-Mila Z. , Obertova J. , Reckova M. , Mego M. , Ladicka M. , Salek T. , Brozmanova K. , Risnyovszka Z. , Koza I. 
Published: March 2020

14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluated the efficacy and toxicity of miniautologous transplantation of LAK in cytokine pretreated patients (pts) with metastatic RCC. Methods: Between May 1998 and July 2005, 29 pts (23M/6F) with metastatic RCC were included. All patients were pretreated with cytokine-based therapy (9 pts with interferon alfa, 9 pts with interferon alfa+5FU+IL-2, 10 pts with interferon alfa+5-FU and 1 patient with IL-2). Median age was 58 years (range 49–71). Patients were assigned into three prognostic groups according to MSKCC prognostic criteria for 2nd line treatment (Motzer et al., 2004). Six, seventeen and six pts had 0, 1 and 2–3 risk factors, respectively. Median number of metastatic sites was 2 (range 1–6). 9 pts had liver, 12 bone and 2 patients had cerebral metastases. Median time from cytokine treatment to LAK therapy was 9 months (range 0–41). Periferal blood stem cells (PBSC) were isolated. Part of the PBSC was used to isolate mononuclear cells (MNC). The MNC were incubated in the presence of IL-1, IL-3, IL-6, GM-CSF and SCF. After the conditioning regimen with cyclophosphamide (2g/m2), the PBSC and MNC were pooled and reinfused. Results: Minor response was achieved in 2 pts (7%), 95% CI (0–16%). Overall survival was 8.0 months (5.0–9.8). Median survival 10.0, 8.0 and 9.7 months was achieved in patient’s group with 0, 1 and 2–3 MSKCC risk factors, respectively. Treatment was well tolerated. Four pts (14%) experienced febrile neutropenia after the conditioning regimen. There was no Grade 3–4 non-hematological toxicity and no treatment related death. Conclusions: Despite good tolerability and feasibile administration, the results of our trial do not warrant further study of herein presented experimental treatment. However, new treatment aproaches are needed. No significant financial relationships to disclose.
Prostate brachytherapy post implant dosimetry: Timing matters
Authors: Minehan K. J. , Furutani K. , McNamara K. , Groshek D. , Mitchell E. , Price M. , Emme M. , Harms T. 
Published: March 2020

14597 Background: Permanent seed implant (PSI) brachytherapy is a common treatment modality for low-risk prostate cancer. Post implant dosimetry (PID) is utilized to asses the quality of the implant. Significant prostate swelling occurs as a result of the implant procedure, and this swelling subsides over time. PID completed on Day 0 after the implant procedure captures the prostate swelling from the procedure. Conversely, PID completed one month later does not have this swelling. PID can therefore show great variation, depending on the timing of the analysis. It is hypothesized that PID completed on Day 0 demonstrates lower dosimetric parameters than PID completed one month later. Methods: Thirteen low risk prostate cancer patients, (Stage ≤ T2, PSA < 13.9, Gleason Score ≤7) were implanted with 125Iodine seeds, with a prescription dose of 145Gy to the prostate plus a 5mm margin. Computed Tomography (CT) PID was completed for each patient on day 0 and on average 33 days following the implant. The prostate was contoured on each axial CT image and the data was analyzed using commercially available PSI planning software. The dose which encompassed 90% of the prostate volume (D90) was calculated for day 0 and day 33 PID. Results: On average, the prostate volume contoured was larger on day 0 PID (Avg. 44.9 cc; range 19–97 cc) compared to day 33 PID (Avg. 38.9 cc; range 18–59 cc) (P = 0.068). The D90 values however, were significantly higher on day 33 PID (Avg.163.7 Gy; range 125–212 Gy) than on day 0 PID (Avg.149 Gy; range 112–166 Gy) (P = 0.003). This D90 relationship was even demonstrated paradoxically in two patients whose contoured prostate volume was larger on the day 33 PID as compared to the day 0 PID. Conclusions: Timing does matter in the analysis of post implant dosimetry for PSI brachytherapy. The D90 values were significantly greater on day 33 PID compared to Day 0 PID while the contoured prostate volumes were not. Future studies which use PID planning to evaluate implant quality should specify the timing of the PID, as this would facilitate cross study comparison. No significant financial relationships to disclose.
Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanese patients with hormone refractory prostate cancer
Authors: Fujisaka Y. , Fujiwara Y. , Yamada K. , Shimizu T. , Horiike A. , Yamamoto N. , Yamada Y. , Matsuoka N. , Fujimoto H. , Tamura T. 
Published: March 2020

14602 Background: Endothelin (ET)-1 and its primary receptor, the ETA receptor, contribute to tumor cell growth, survival, angiogenesis and invasion. Atrasentan is a highly potent, selective ETA receptor antagonist. This study assessed safety and pharmacokinetics (PK) in Japanese patients with hormone refractory prostate cancer. Methods: This open-label, single-center Phase I trial evaluated the safety and PK of escalating oral atrasentan doses (2.5, 10 or 20 mg) given daily on day 1 and day 4 through 27 (except day 2 and 3). Dose-limiting toxicity (DLT) was defined as Grade 3 or greater adverse events related to study drug. Results: Eighteen patients, aged 54–74 (median; 66) were treated in cohorts of 6 patients each. The compliance of all patients was 100%. The most common toxicities were rhinitis, peripheral edema, headache, hypotension and anemia, all of which were well tolerated. These events were consistent with the anticipated vasodilatory effects or with a hemodilution effect of the study drug. DLTs were not observed. Atrasentan was rapidly absorbed following oral administration of 2.5 to 20 mg, maximum plasma concentrations averaged from 0.4 to 0.8 hours. After peaking, plasma concentrations declined bi-exponentially with a terminal half-life of approximately 25 hours. In the 10 mg dosing group, the steady-state maximum plasma concentration (Cmax) and the area under the curve (AUC0–24h) averaged 135.5 ng/mL and 533 ng h/mL, respectively. The Cmax and AUC values generally increased linearly with increasing dose after single- and multiple-dose administration. Compared to baseline, PSA decreased 50% or more in 1 patient (20 mg) and increased 25% or more in 10 patients (2.5 mg;2, 10 mg;5, 20 mg;3). The PSA of the remaining 7 patients (2.5 mg;4, 10 mg;1, 20 mg;2) ranged from < 25% increase to < 50% decrease. Fourteen patients continued on study drug in an extension study. Conclusions: Atrasentan is well tolerated, with no dose-limiting adverse events observed up to 20 mg in Japanese patients. The main adverse events are consistent with the vasodilatory effect of the drug. PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing. No significant financial relationships to disclose.
Phosphodiesterase (PDE) inhibitors reduce in vitro proliferation of prostate primary cells but do not interfere with growth of prostate carcinoma cell lines
Authors: Pernkopf D. G. , Untergasser G. , Berger P. , Plas E. 
Published: March 2020

14604 Background: PDE 5 is highly expressed in cavernosal and prostatic tissue. The mechanism of PDE-5 inhibitors on cavernosal tissue is well established but the effects of PDE-5 inhibitors on prostatic cells are unknown. The aim of this study was to analyze in vitro effects of PDE-5 inhibitors on prostate primary cells, fibroblasts (PrSC), basal epithelial cells (PrEC) and prostate cancer cell lines. Methods: Cultivated PrEC and PrSC, immortalized BPH cells (BPH 1), androgen dependent (LNCaP) and androgen independent (PC3) prostate carcinoma cell lines were exposed to increasing concentrations of commercially available PDE 5 inhibitors Sildenafil (Sil), Tadalafil (Tad), Vardenafil (Var). After incubation for 3 days cell viability was determined by a WST-1 assay (Roche-Biochemicals). Cells were evaluated morphologically by invert-light microscopy. PDE-5 protein concentrations were determined by western blot analyses and tissue distribution of PDE-5 by immunohistochemistry (IHC) with a polyclonal antiserum. Results: None of the PDE-5 inhibitors induced cell proliferation. Significant decreases in proliferation and viability were observed at high concentrations (1 mg/ml) of all substances in PrSC and PrEC. In PrSC, proliferation rate decreased to 37.7% in Sil, to 16.9% in Tad and to 63.7% for Var as compared to controls. In PrEC, proliferation decreased to 72.7%, 21.6% and 84.4% for Sil, Tad and Var, respectively. At 0.1 mg/ml only Tad reduced proliferation significantly to 57.4%. Moreover, Tad induced neuroendocrine-like morphology in some PrEC. High protein concentrations of PDE 5 were observed in PrEC, low concentrations in PrSC but none in cancer cells. Conclusions: Sil, Tad and Var inhibit proliferation of prostate primary cells in vitro. Tad showed highest inhibition. Tumor cells were insensitive to PDE-5 inhibitors, due to the lack of PDE-5 protein. It seems unlikely that any of these substances increases proliferation of prostate carcinoma. Tad induced neuroendocrine-like morphology in some basal PrEC indicating effects on cellular differentiation. No significant financial relationships to disclose.
Undetectable PSA level following prostate brachytherapy
Authors: Barrett W. L. 
Published: March 2020

14609 Background: Following radical prostatectomy for adenocarcinoma of the prostate, a long term undetectable PSA level is associated with cure. Patients with persistent long term detectable but low PSA levels after prostate radiation are frequently thought to be cured with the assumption that residual benign prostate tissue may produce low levels of PSA in the absence of cancer. There is not an established PSA nadir following radiation therapy that is universally associated with cure. In our institutional experience PSA nadirs of less than or equal to (≤) 0.2 and ≤ .5 have been associated with disease control by the ASTRO consensus statement in 95% and 89% of patients respectively. None of our patients who have obtained an undetectable PSA following prostate brachytherapy have subsequently gone on to have a rising PSA. The purpose of this study is to determine the frequency of undetectable PSA following prostate brachytherapy. Methods: 209 consecutive patients were treated with radioactive Iodine 125 seed implantation alone as definitive treatment between 1/96 and 1/03. No patients received external radiation therapy or hormone therapy. Post treatment PSA levels were reviewed to ascertain the number of patients achieving undetectable PSA levels, PSA of ≤ 0.2, PSA ≤ 0.5, and PSA failure based on the ASTRO consensus statement definition. Results: At a median follow up of 80 months (range 36 to 120), 75 patients (36%) have achieved and maintained an undetectable PSA level. 27 patients (13%) have experienced biochemical failure by the ASTRO definition. 72% and 78% have achieved and maintained PSA nadirs of ≤ 0.2 and ≤ 0.5 respectively. Conclusions: There has been difficulty in comparing treatment results in patients treated with radical prostatectomy compared to radiation therapy for cancer of the prostate due to the different PSA patterns following the different treatments and the varying definitions of success or failure. Undetectable PSA level after prostate brachytherapy appears in our experience to be consistently associated with disease free status based on the most stringent definition of disease free status following prostatectomy. No significant financial relationships to disclose.
Zoledronic acid in patients with adenocarcinoma of the prostate M1
Authors: Calais Da Silva F. M. , Calais Da Silva F. E. 
Published: March 2020

14623 Background: There is presently clinical evidence that confirms the value of bisphosphonates in metastatic bone disease. Studies have demonstrated that bisphosphonates may reduce bone morbidity and pain, thus increasing the quality of life of patients with multiple mieloma and bone metastases in breast cancer. In metastatic prostate cancer several oral and i.v. bisphosphonates have demonstrated a symptomatic improvement. Zoledronic acid is a bisphosphonate that has proved to diminish the skeletal related events (SRE) in metastatic prostate cancer. Methods: We have initiated a study with two types of patients: patients with bone metastases, With and Without pain, with the primary objective of measuring the efficacy of zoledronic acid in these patients, assessing the time to reduce the pain score or decrease the analgesic score in symptomatic patients and SRE in those non symptomatic, evaluating the time to bone pain and SRE. We started zoledronic acid 4 mg i.v. monthly. Results: We evaluated 87 patients, 16 were not evaluable and 71 evaluable, with at least 3 administrations. From these 70 patients, 11 had no pain with a median follow-up of 9.7 months (3–22 months) out of which 6 (54%) remain pain free (3–18 months). No SRE were registered. The remaining 60 patients had pain at initiation: 24 (40%) were not responsive and 36 (60%) were responsive and registered pain palliation, within an average follow-up of 9.2 months (3–22 months). The average time to response was 3.2 months (1–8 months) and average response duration was 4 months (1–11 months). Only 2 patients required administration of Samarium i.v.; no other SRE. Conclusions: Zoledronic acid is and I.V. bisphosphonate effective in the palliation of pain in patients with bone metastases, which produces decrease of pain and analgesic score with a fast response - in average 3.2 months - and a therapeutic efficacy maintained in average for 4 months. In high-risck patients with bone M1 but without pain, it was also verified that 54% kept pain free at the end of 9.2 months and 45% only started to feel pain again at 6 months. No significant financial relationships to disclose.
Interstitial high dose rate (HDR) brachytherapy alone for early stage prostate cancer
Authors: Mark R. J. , Anderson P. J. , Neumann T. , Nair M. 
Published: March 2020

14633 Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) technique has been reported with results comparing favorably to surgery and External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial implant is combined with EBRT. There is little published data on HDR alone. We report our results with HDR alone. Methods: Between 1997 and 2006, 167 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant. There were no Gleason Score or PSA exclusions. No patient received EBRT or Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes ranged from 42 cm3 to 196 cm3. Treatment volume included the prostate and seminal vesicles in all cases. Our protocol for HDR alone, has called for two HDR Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12–16) were followed, and limited to ≤ 105% of the prescription dose. Results: With a median follow-up of 64 months (range: 6 months to 112 months), PSA disease free survival was 89.8% (150/167). Urethral stricture requiring dilatation has developed in 4.2% (7/167) of patients. Urinary stress incontinence has occurred in 3.6% (6/167). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.6% (6/167) Grade 2. RTOG late rectal toxicities were: 0.6% (1/167) Grade 4, 0% Grade 3, 1.8% (3/167) Grade 2, and 2.4% (4/167) Grade 1. There have been no cases of rectal incontinence to date. Conclusions: Five year results with HDR implant alone compare favorably to EBRT, LDR ± EBRT, and HDR + EBRT, both with regard to PSA disease free survival, and complications. HDR offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, bladder and rectal complications appear to be significantly reduced. No significant financial relationships to disclose.
The importance of age as a prognostic factor in corpus cancer
Authors: Husain A. , Karnik Lee N. , Cheung M. K. , Osann K. , Chen L. M. , Chan J. K. 
Published: March 2020

15005 Background: To determine the prognostic factors that influence the survival of younger women diagnosed with uterine cancers. Methods: Patients with a diagnosis of uterine cancer were isolated from the Surveillance, Epidemiology, and End Results (SEER) cancer database from 1988–2001 and demographic and clinico-pathologic data were collected. Patients in the database were stratified by age at diagnosis into two age groups: ≤40and >40 years old. Disease specific survival was calculated using Kaplan-Meier estimates. Results: Of the 51,471 women diagnosed with uterine cancer in the study period, 2076 patients were ≤40 and 49,395 were >40 years old. The mean age in the younger group was 35.6 and that of the older group was 65.2. The overall distribution by stage was Stage I-76%, II-8%, III-7% and IV-9%. Younger patients were more likely to be non-white (30% vs 18%, p < 0.05), have earlier stage disease (79% vs 75%, p < 0.05), grade 1 lesions (48% vs 36%, p <0.05) and sarcomas (16% vs 8%) compared to their older counterparts. The overall disease specific 5-year survival demonstrated that younger patients (≤40 years old) had a significantly improved survival prognosis in comparison to older women (93% versus 86%; p < 0.0001). This survival difference remains significant after adjusting for stage, race, surgical treatment, and radiation treatment. Subgroup analysis revealed no statistical difference in outcome between the two age groups for patients with clear cell histology. There also was no statistical significance in survival for patients with grade 2 or 3 lesions and advanced stage disease. Conclusions: Our large population based study demonstrates that younger patients (≤40) have an overall survival advantage compared to women >40 years. This difference remains significant when adjusted for stage, race, surgical treatment, and radiation treatment. Women with clear cell cancers of the uterus appear to have a poor prognosis independent of age. No significant financial relationships to disclose.