bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line treatment with bevacizumab (B) and high dose (HD) bolus aldesleukin (IL-2) in metastatic renal cell carcinoma (mRCC) patients (Pts)
Authors: Ernstoff M. S. , Regan M. M. , McDermott D. F. , Sosman J. A. , Dutcher J. P. , Clark J. I. , Crocenzi T. S. , Ochoa A. , Atkins M. B. 
Published: March 2020

15524 Background: The rationale for combining HD IL-2 with B includes potential synergistic immune interactions, non-overlapping toxicities, and potential for added clinical benefit. We have initiated a multi-center phase II study designed to estimate the efficacy of combination therapy of standard HD IL-2 and B therapy in mRCC pts. Methods: Pts with histologically confirmed mRCC, predominantly clear cell histology, measurable or evaluable disease, KPS of =80%, adequate end organ function for HD IL-2, and no underlying coagulopathy or thrombotic event are eligible for this study. One cycle consists of 84 days. B (10 mg/kg) IV is given every 2 wks beginning 2 wks prior to the first dose of IL-2. B is dosed 1 hr prior to initiating IL-2 on days IL-2 is given. HD IL-2 (600,000 IU/kg) IV Q8 hours (maximum 28 doses) is given during two 5-day courses separated by 9 days (starting on day 15 and 29). Results: We report the results of the first 15 of a planned 60 pts. The median age is 54 (range 40–73) with 9 men and 6 women. 14 pts have a MSKCC intermediate prognostic score, one pt has a poor prognostic score. In the first cycle, the median number of B doses was 7 of a planned 7 (range 2–7) and the median number of IL-2 doses was 17 of a planned 28 (range 6–26). There has been one treatment related death from unresponsive hypotension which occurred during the second cycle. Typical IL-2 toxicities have been noted thus far. Among a variety of correlative studies, we evaluated the serum L- ornithine (L-O) level, a byproduct of arginase-mediated arginine metabolism that has been shown to inversely correlate with TCR? chain expression. L-O level are significantly elevated in RCC pts possibly due to VEGF stimulation of arginase production. In 4 patients tested to date, peripheral blood L-O levels have dramatically decreased over the course of therapy. Conclusions: HD IL-2 and B can be given safely and may impact on immune regulatory pathways. [Table: see text]
Adjuvant chemotherapy in lymph node positive bladder cancer
Authors: Gofrit O. N. , Stadler W. M. , Zorn K. C. , Silvestre J. , Shalhav A. L. , Zagaja G. P. , Steinberg G. D. 
Published: March 2020

15526 Background: Lymph node-positive bladder cancer is a systemic disease in the majority of patients. Prescribing adjuvant chemotherapy shortly after surgery, when tumor burden is low seems reasonable, yet there is no proof that this treatment strategy improves survival. In this retrospective study, we compared the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy. Methods: Sixty-seven patients with lymph node positive bladder cancer (pN1 in 26 patients and pN2 in 41) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but deferred by 32 (48%). The two groups were similar in performance status, postoperative complication rate and N stage but deferring patients were on average 4 years older and had a more advanced T stage. Results: Adjuvant chemotherapy was well tolerated with 28/35 patients (80%) completed all 4 cycles. Median overall survival of patients given adjuvant chemotherapy was 48 months compared to 8 months for deferring patients (hazard ratio 0.13, 95% CI 0.04–0.4, p<0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting overall survivals (hazard ratio 0.2, p<0.0001). Subgroup analysis demonstrated that chemotherapy provided survival benefit for patients with pN2 disease but not for patients with pN1 disease (p=0.0001 and p=0.235 respectively). Conclusions: This retrospective real-life study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer, especially when more than one lymph node is involved. No significant financial relationships to disclose.
Prediction of PSA spikes by isotope and patient age following permanent prostate brachytherapy
Authors: Bostancic C. , Merrick G. S. , Butler W. , Wallner K. , Allen Z. , Galbreath R. , Lief J. , Gutman S. 
Published: March 2020

15535 Background: To evaluate prostate specific antigen (PSA) spikes (bounces) following permanent prostate brachytherapy in low-risk patients randomized to Pd-103 or I-125. Methods: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing Pd-103 with I-125 for low-risk disease. Sixty-one patients (37.2%) received short course cytoreductive androgen deprivation therapy (ADT). No patient received supplemental XRT. The median follow-up was 5.4 years. All patients were implanted at least 3 years prior to analysis. On average, 10.1 post-treatment PSA’s were obtained per patient. Biochemical disease-free survival was defined as a PSA = 0.40 ng/mL after nadir. A PSA spike was defined as a rise of = 0.2 ng/mL followed by a durable decline to pre- spike levels. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors for a PSA spike. Results: Forty- four patients (26.9%) developed a PSA spike including 45.7% (21/46) of the hormone naïve I-125 patients and 14.0% (8/57) of the hormone naïve Pd-103 patients. In hormone naïve patients, the mean time between implant and spike was 22.6 months and 18.7 months for I-125 and Pd-103 patients, respectively. In patients receiving neoadjuvant ADT, the incidence of spikes was comparable between isotopes (28.1% for I- 125 and 20.7% for Pd-103). The incidence of spikes was substantially different in patients < 65 vs = 65 years of age (16.3% vs. 38.5%). In multivariate Cox regression analysis, patient age at implant (p < 0.001) and isotope (p = 0.002) were significant predictors for spike. Conclusions: In low-risk prostate cancer patients, PSA spikes are most common in patients implanted with I-125 and/or younger than 65 years of age. Differences in isotope-related spikes are most pronounced in hormone naïve patients. No significant financial relationships to disclose.
Effects of zoledronate (Z) on bone mineral density (BMD) among African Americans (AA) with advanced prostate cancer, without skeletal metastases, recieving androgen ablation therapy
Authors: Kipping K. L. , Bennett C. , Evens A. , Munshi H. , Jovanovic B. , Gallot L. 
Published: March 2020

15539 Background: Prostate cancer can be detrimental to bone health: it affects older men who have a higher risk of osteoporosis; common treatment is androgen ablation which can cause bone loss, and it frequently metastasizes to the bones. These issues are especially important in AA men, who present with higher rates of advanced disease and use of androgen ablation than whites. One study found beneficial effects of Z on the bone health of men with prostate cancer, it included only 106 men, and few were AA (Smith M, Journal of Urology).We wanted to evaluate the effects of Ca/Vitamin D ± Z on skeletal related events and BMD on AA and white men with prostate cancer who are receiving androgen ablation therapy. Methods: Prostate cancer patients receiving at least 3 months of androgen ablation were eligible. Exclusion criteria: use of bisphosphonates in last 12 months, abnormal liver/ kidney function, or prior bone disease. 41 patients have been randomized, 51% are AA. Patients on the Z arm receive 4 mg IV infusion of Z q 3 months over one year. Patients have bone densities at baseline and 13 months. Results: Interim analysis is available for patients who have completed study as of Jan 2007. 3 patients were taken off study (1 due to secondary cancer, 2 due to patient withdrawal).One patient withdrew due to jaw pain, follow up did not identify osteonecrosis. Two patients had lesions that may have been bone metastases, follow up testing was inconclusive. At treatment end, Z-treated patients had higher BMD scores than control group patients. AA patients treated with Z also showed increased BMD values at 13 months. Conclusions: Z appears to have a positive effect on BMD in AA men with prostate cancer- potentially more beneficial than among the effect previously reported for white men with prostate cancer. AA men with prostate cancer receiving androgen ablation should be considered for Z therapy to improve bone health. [Table: see text] No significant financial relationships to disclose.
Prognostic risk factors to predict final pathohistology in patients undergoing radical salvage prostatectomy for locally recurrent prostate cancer after radiation therapy
Authors: Pfister D. , Ohlmann C. , Sahi D. , Engelmann U. , Heidenreich A. 
Published: March 2020

15544 Background: Radical salvage prostatectomy (sRPE) represents one local secondary treatment option with curative intent in patients failing radiation therapy for localized prostate cancer (PCA). Currently, there are very few studies correlating preoperative clinical and pathohistological variables with final pathohistology of sRPE specimens. It was the purpose of our study to identify prognosticators predicting organ confined and locally advanced PCA. Methods: 45 patients with biopsy-proven locally recurrent PCA underwent sRPE and extended pelvic lymphadenectomy (epLA) via a retropubic approach. Preoperative PSA, PSA doubling time, PSA prior to initial radiation therapy, biopsy Gleason score, number of positive biopsies, cT stage, 11choline PET/CT findings, type of radiation therapy, neoadjuvant androgen deprivation were correlated with the pathohistological stage by uni- and multivariate analysis. Results: A total of 45 patients underwent sRPE and epLA; 16 (35.5%), 12 (26.6%) and 17 (37.8%) patients had undergone external beam radiation (EBRT), HDR and LDR brachytherapy, resp. The mean preop. serum PSA was 7.8 (2–24) ng/ml; mean biopsy Gleason score was 5.6 (4–9). We did not encounter significant intraoperative compliations, the mean blood loss was 490 (200–950) ml. A mean of 19 (10 - 32) lymph nodes were removed. Pathohistology showed stage pT1–2pN0 in 27 (60%), stage pT3a/b and pTxpN1 PCA in 9 (20%) and 9 (20%) of patients, respectively. Positive surgical margins were identified in 5 (11%) patients. By multivariate analysis the parameters significantly associated with organ confined PCA sRPE are PSADT > 12 months, = 50% positive biopsy cores, biopsy Gleason score = 7 and previous LDR brachytherapy (pT1–2pN0R0 in all men); pre-radiation and preoperative PSA, PET/CT findings had no significant impact with final pTpN-stage. Conclusions: SRPE can be performed with a low morbidity in biopsy proven locally recurrent PCA after radiotherapy. The identified prognostic parameters will help to select patients most suitable for a local secondary surgical approach with curative intent. Especially in patients with local relapse following LDR brachytherapy sRPE represents a valuable treatment option. No significant financial relationships to disclose.
A phase II trial of oxaliplatin and docetaxel in patients with androgen independent prostate cancer (AIPC) who have progressed to two prior regimens of chemotherapy
Authors: Feinstein T. , Appleman L. J. , Friedland D. M. , Jacobs S. A. , Ferri W. A. , Earle M. F. , Hyoung K. D. , Strausser H. , Corgnati S. , Chatta G. S. 
Published: March 2020

15545 Background: Single agent docetaxel has demonstrated survival benefit in AIPC. In a phase I study of single agent oxaliplatin at our institution, two patients with AIPC experienced a substantial and durable reduction in PSA. Thus, we hypothesised that a combination of oxaliplatin and docetaxel maybe beneficial in AIPC. Methods: This single arm phase II trial in patients with previously treated (0–2 regimens) and progressive AIPC commenced in June 2005, with the objectives of evaluating PSA response rates, progression free survival, and the toxicity (tolerance/safety) of the regimen. In patients with soft tissue disease, measurable responses were assessed by RECIST criteria. Using Simon stage II design, a total of 37 patients with AIPC will be accrued. No prior treatment with platinum was allowed. Treatment consisted of oxaliplatin (110 mg/m2) and docetaxel (60 mg/m2), administered intravenously every 21 days for a maximum of 6 cycles. Results: 27 men have been enrolled to date: median age 66 yrs (56–84). 21 of 27 men have completed at least two cycles of the above regimen, and are evaluable. Prior therapies included antiandrogens (100%); ketaconazole (14%); docetaxel alone or in combination (27%); anthracyclines (27%); and vaccine (5%). Median PSA at baseline was 88 ng/ml (range 2.2–3559.4). 62% of patients received all six cycles. PSA declines of ≥50% were noted in 11 of 21 patients: 3 of 8 responders being chemo-naïve; and 8 of 13 with prior chemotherapy exposure. In addition, 4 of 11 patients with measurable disease at baseline, had a partial response. Treatment was well tolerated with no treatment-related deaths. The most significant grade 3/4 adverse event (AE) was neutropenia (43%). Grade 2 or less fatigue (66%), neuropathy (53%) diarrhea (47%), nausea (41%), anorexia (29%), thrombocytopenia (12%) and anemia (6%). Conclusions: The combination of oxaliplatin and docetaxel has promising activity in both chemo-naïve and previously treated AIPC. This 2-stage study will accrue a total of 37 patients. Final analysis will include time to progression, duration of response, and median survival. [Table: see text]
Phase I study of picoplatin and docetaxel (D) with prednisone (P) in patients (pts) with chemotherapy-naive metastatic hormone refractory prostate cancer (HRPC)
Authors: Roman L. , Karlov P. , Kaprin A. , Gladkov O. , Breitz H. 
Published: March 2020

15546 Background: Picoplatin is a sterically hindered platinum analogue specifically developed to overcome platinum resistance and to improve on the safety and efficacy of other platinum-based drugs. In >600 pts, picoplatin had single-agent activity in prostate, lung, ovarian and other malignancies with rare clinically significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4), even in platinum pretreated pts. An objective response rate of 20% and a PSA response rate of 25% were observed following 120 mg/m2 picoplatin q 3 wk in 20 chemotherapy-naïve pts with HRPC. D + P leads to superior survival, increased PSA response and improved quality of life in HRPC pts. Picoplatin has demonstrated synergy with taxanes in pre-clinical studies. Thus the current study is designed to investigate D + P + picoplatin in chemotherapy-naïve pts with metastatic HRPC. Methods: Pts with documented progression of metastatic disease during adequate hormonal therapy, ECOG performance status of 0 or 1 and preserved organ function received D, 60 mg/m2 q 3 wks + P, 5 mg, po bid + picoplatin. Picoplatin has been given to date to sequential cohorts of subjects at 60 mg/m2, 80 mg/m2 and 100 mg/m2. Results: 16 pts have been enrolled and have received up to 8 cycles of therapy. Therapy has been well tolerated. No dose limiting toxicity has been observed. Dose reduction for thrombocytopenia has been required in 1 pt, but there has been no cumulative myelotoxity. 7 pts in the first 3 dose cohorts have been evaluated for efficacy after 4 cycles (12 weeks): at doses below the maximum tolerated dose, there were 3 PSA responses and 1 objective partial response. Dose escalation continues. Conclusion: Picoplatin can be safely administered with D + P in chemo-naïve pts with HRPC. A phase 2 study of this combination will begin when an optimal, safe dose is defined. No significant financial relationships to disclose.
Association of weekly gemcitabine to conformal radiotherapy as organ-sparing strategy in locally advanced or relapsed bladder cancer
Authors: Carillio G. , Alì M. , Mazzola A. , Bagnato S. , Todaro A. , D’Agostino A. , Girlando A. , Aiello R. , Fallica G. , Chiarenza M. , Caruso M. 
Published: March 2020

15570 Background: Radical surgery is considered the only curative option for locally advanced or relapsed bladder cancer. However, the uncertain prognosis of disease and the poor quality of life due to lack of bladder reservoir require further investigation on possible therapeutic approaches. Methods: This trial has been designed for testing safety and activity of dose-escalating gemcitabine associated to concomitant conformal radiotherapy for locally advanced or relapsed bladder cancer. Patients received radiotherapy at 2 Gy per day to reach a total dose of 60 Gy over 6 weeks. Gemcitabine was administered once-a-week as one-hour IV infusion before starting the radiation treatment. The first explored dose of drug was 300 mg/m2 and the escalation was planned through a Fibonacci modified method by subsequent increases of 100 mg/m2 until definition of the dose-limiting toxicity (DLT). The recommended dose for future phase II study was one level inferior to the reached maximum tolerated dose (MTD). Results: Eighteen patients with median age of 72 years entered the study, half of whom affected by locally advanced tumours, the remainders by recurrence after conservative surgery. The majority of the latter initially had pT2 (UICC staging) muscle invasive transitional cell carcinoma. Twelve patients were treated with weekly gemcitabine at 300 mg/m2 without appearance of any DLT. Among the first 3 patients receiving the dose level of 400 mg/m2, one patient had grade 4 neutropenia. Further 3 patients were enrolled for testing the above dose level, but one of them experienced bowel perforation, therefore the established MTD was 400 mg/m2. The recommended dose of weekly gemcitabine was 300 mg/m2. Effectively, we could observe 11 (61%) pathological complete responses (pCR) confirmed by bladder mapping two months after treatment completion. Nine pCR (82%) occurred in the patients with locally advanced therapy-naïve bladder cancer. Patients with conserved bladders had excellent function, without hematuria, urgency or incontinence. Conclusions: The association of weekly gemcitabine to conformal radiotherapy provides a new alternative to radical surgery approach and strongly supports the organ-sparing strategy for locally advanced bladder cancer. No significant financial relationships to disclose.
Validation of quantitative fluorescence imaging analysis (QFIA) of β-catenin in archived prostate tissues for cancer biomarker discovery
Authors: Hemstreet G. P. , Casale G. P. , Huang D. , Tian J. , Simpson M. A. , Kaleem Z. , Smith L. M. , Elkahwaji J. E. , Johansson S. L. 
Published: March 2020

15575 Background: The objective of this study was to develop a sensitive tissue proteomic assay for quantifying proteins (e.g. β- catenin) in tissues and prostate core biopsies by QFIA. A second objective was to apply the validated methodology to quantify other biomarkers for prostate cancer risk assessment, and to study oxidative stress in BPH, prostate cancer, the cancer field, and in inflammatory prostatitis in animals and human prostatitis. Methods: Biopsies from controls and cancer patients were depariffinized, the antigen retrieved, and labeled with a robotic BioGenex Stainer with a primary mouse monoclonal antibody (1/100) to β-catenin. A secondary goat anti-mouse IgG antibody (2° Ab 1/100) coupled with Alexa Fluor 568 was used as the indicator system. The Leica Fluorescence Microscope was calibrated and standardized with fluorescence beads, LNCAP cells, and BPH tissue sections. QFIA of β-catenin was validated by RPPA methacarn fixed tissues. Adjacent 4-micron tissue sections were analyzed by QFIA for total β-catenin content by RPPA. Results: Reproducibility was 10% or less for the LNCAP cells and BPH tissue controls. Adjacent tissue sections assayed by QFIA and RPPA exhibited a strong linear correlation (r=.97) as did tissues fixed in methacarn vs.10% buffered-formalin and assayed by QFIA (r=0.84). For the core biopsy specimens the average MPI (AMPI) from 40 to 200 acini was quantified. The AMPI of cancerous acini (CA) compared to nomal acini (NA) was reduced in 37 of 42 cases p<.02. ROC plots revealed that β-catenin expression in NAA identified 42% (95%CI 25 - 52%) of cancer cases, with 88% (95% CI 80%-96%) specificity. The tissue QFIA method was used to quantify oxidative stress biomarkers (MnSOD, HNE, 8-OHdG) and other field disease biomarkers (Connexin42, and UDP-glucose dehydrogenase (UGDH) in BPH, prostate cancer, and in prostatitis. Conclusions: A tissue based QFIA method has been developed for the quantification of β-catenin in prostate core biopsy specimens, and the method has been validated by RPPA. Assay of β-catenin in prostate core biopsy specimens shows promise as a potential biomarker for a profile defining individuals at risk for prostate cancer and studying oxidative stress in relation to the pathogenesis of disease. No significant financial relationships to disclose.
Androgen deprivation therapy does not impact cause-specific or overall survival in high-risk prostate cancer treated with brachytherapy and supplemental external beam
Authors: Allen Z. , Merrick G. S. , Butler W. , Wallner K. , Galbreath R. , Adamovich E. , Lief J. 
Published: March 2020

15578 Background: To determine cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) in high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods: From April 1995 through July 2002, 204 patients with high risk prostate cancer (Gleason score = 8 and/or PSA > 20 ng/mL and/or clinical stage = T2c) underwent brachytherapy with or without supplemental therapies. Of the 204 patients, 193 (94.6%) received supplemental XRT and 119 (58.3%) received ADT (ADT = 6 months n=40 and ADT > 6 months n = 79). Median follow-up was 7.0 years. All patients were implanted at least 4 years prior to analysis. BPFS was defined by a PSA = 0.40 ng/mL after nadir. Multiple clinical, treatment and dosimetric parameters were evaluated for the impact on survival. Results: The ten-year CSS, bPFS and OS were 88.9%, 86.6% and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naïve, ADT = 6 months and ADT > 6 month cohorts (79.7% vs. 95.0% vs. 89.9%, p= 0.032). ADT did not impact CSS (94.0% vs. 87.1%, p=0.983 ) or OS (65.2% vs. 70.3%, p = 0.713). For bPFS patients, the median post-treatment PSA was < 0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent positive biopsies and duration of ADT best predicted for bPFS. OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died with 26 of the deaths due to cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: Androgen deprivation therapy improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact overall survival. No significant financial relationships to disclose.