bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of efficacy of TIP combination (paclitaxel, ifosfamide, cisplatin) as first salvage therapy for patients with relapsed germ cell tumors in a poor prognosis group
Authors: Mardiak J. , Rejlekova K. , Mego M. , Rajec J. , Sycova-Mila Z. , Obertova J. , Salek T. , Reckova M. 
Published: August 2020

e16049 Background: The efficacy of TIP appears to be suitable salvage therapy for patients with relapsed germ cell tumors (GCTs) with good prognostic features.The aim of our study was to determine the efficacy of TIP as first salvage therapy for patients with relapsed GCTs with poor prognostic features. Methods: Thirty seven patients with relapsed GCTs were treated with TIP as first salvage therapy. Sixteen (43%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen) and 21 (57%) patients had poor prognostic features (either extragonadal site or incomplete response to induction chemotherapy regimen). Four cycles of paclitaxel (175 to 250 mg/m2), ifosfamide 6 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with GC-SF support, followed by resection of resectable radiographic residua. Results: Ten (69%) out of 16 patients with good prognostic features achieved a favorable response to TIP, and all 10 (100%) patients achieved complete response (CR). Six (60%) of the favorable responses remain durable at a median follow-up of 50,6 months. 9 (43%) of 21 patients with poor prognosis achieved a favorable response to chemotherapy, from whom only 1 (10%) patient achieved CR, but 5 patients achieved durable response at a median follow-up duration of 60,6 months. Estimated 2-year overall survival rate (OS) for patients with good prognosis was 56% (95 % CI 54–100%) and 33% (95% CI 21–68%) for patients with poor prognosis. Despite this results, estimated 5-year OS was even more positive for patients with poor prognosis 19% (95% CI 15–61%) comparing to 13% (95% CI 23–80%) for patients with good prognosis. Conclusions: Demonstrated long-term survival of patients with poor prognosis in our nonrandomised study with limited number of patients refers to the TIP being suitable therapy also for patients with relapsed GCTs with poor prognosis. These results warrant the need to continue investigation of real effectiveness of TIP as a first salvage therapy even for patients with poor prognostic features. No significant financial relationships to disclose.
Bortezomib therapy for prostate specific antigen (PSA)-only relapse after definitive local therapy
Authors: Turner J. S. , Chen C. S. , Butler W. , Bearden J. , Garrett-Mayer E. , Onicescu G. , Kraft A. S. 
Published: August 2020

e16053 Background: We conducted a single arm, phase II trial of single-agent bortezomib, a proteasome inhibitor, in patients with prostate cancer with biochemical recurrence (PSA relapse) after definitive local therapy. Eligible patients had previous radical prostatectomy and/or radiation therapy (including brachytherapy), and a rising PSA over 1 ng/mL without bone scan evidence of metastasis. The primary goal of this study was to determine the PSA response to single agent bortezomib. Secondary goal was to identify the time to PSA relapse after bortezomib therapy defined as time from nadir to PSA >1ng/ml. Methods: Treatment was composed of bortezomib 1.3mg/m2 IV on days 1,4,8,11 then 10 days off for the first two cycles. The third cycle was comprised of weekly bortezomib therapy for three out of four weeks. Sixteen patients were enrolled and treated at 4 sites with13 evaluable patients. Results: Median baseline PSA was 12.0 ng/ml. 3 of 13 patients (23%) achieved complete responses and 1 a partial response (PR) for a response rate of 30% (95% CI: 0.09 –0.61). Median time to PSA relapse in these 3 patients was 6.0 months. Linear longitudinal modeling was used to compare the rate of increase in PSA prior to treatment versus during treatment with bortezomib and found that treatment significantly decreased the slope of log PSA during treatment, slowing PSA rise (p = 0.003). The major toxicity associated with bortezomib therapy was peripheral neuropathy (7 pts, grade 3 in 3 pts) requiring dose reductions in 3 cases and discontinuation of therapy in 4 patients. Other toxicities included non-neutropenic infections (shingles in 2 pts), 1 small bowel ileus (grade 3), and 1 case of thrombocytopenia (grade 3). Conclusions: In a small number of patients there was a 30% PSA response rate to single agent bortezomib therapy. Further investigations using bortezomib as a single-agent or in combination are warranted in this patient population. No significant financial relationships to disclose.
Prognostic and predictive values of carbonic anhydrase IX (CAIX) and pathologic features in patients with metastatic clear cell renal cell carcinoma receiving targeted therapy
Authors: Choueiri T. K. , Regan M. , Oh W. , Clement J. , Amato A. , McDermott D. , Cho D. , Atkins M. , Signoretti S. 
Published: August 2020

e16067 Background: Tumor Carbonic Anhydrase IX (CAIX) expression and histologic features can predict outcome in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy. We sought to investigate the prognostic and predictive utility of such features in patients receiving VEGF-targeted therapy. Methods: We identified 118 patients with mRCC initiating first- line VEGF-targeted therapy including 94 with clinical data, clear cell histology and available tissue. Tumors were evaluated for specific histologic features and for CAIX expression by immunohistochemistry using the MN75 antibody. The relationship between these pathology findings and tumor shrinkage and other treatment outcomes was assessed. Results: Higher tumor clear cell component was independently associated with greater tumor shrinkage (p=0.02), response (p=0.02) and treatment duration (p=0.02). Patients with high vs. low tumor CAIX expression had mean tumor shrinkages of -12% vs. -5%, respectively (p=.38). There was heterogeneity in tumor responsiveness to sunitinib or sorafenib according to CAIX status (p=0.055 for interaction): mean shrinkage was -17% vs. -25% (mean difference +8%, 95% CI -14% to +31%) for sunitinib-treated patients with high vs. low tumor CAIX expression compared to -13% vs. +9% (mean difference -22%, 95% CI -42% to -1%) for sorafenib-treated patients. Conclusions: Patients with higher clear cell component in their tumors are likely to experience superior clinical benefit from VEGF-targeted therapy. Although CAIX expression was not found to be of prognostic value in patients with clear cell mRCC treated with VEGF-targeted therapy, it may be a predictive biomarker for response to sorafenib treatment. [Table: see text]
Microvesicular-mediated gene transfer of prostate tumor markers
Authors: Renzulli J. F. , Dooner G. , Owens C. , Colvin G. , Dooner M. , Del Tatto M. , Goldstein L. , Quesenberry P. 
Published: August 2020

e16076 Background: Microvesicles have been a subject of research for many years. Recent work has focused on the potential for cancer vaccines via microvesicles. It has also been demonstrated that various cell-specific phenotypes can be transferred from one cell type to another through microvesicle transfer. Studies in our laboratory have demonstrated that co-culture of murine lung tissue with marrow cells across a cell impermeable membrane can induce elevations in lung-specific mRNA expression in human donor marrow stem cells. Our objective is to determine whether there is transfer of genetic or transcriptional factors via microvesicles from human prostate cancer cells to fresh human marrow cells. Methods: Fresh prostate tissue was harvested from surgical specimens following radical retropubic prostatectomy. Samples were histologically confirmed to contain prostatic adenocarcinoma. Co-cultures were established using a transwell system in which 0.05–0.100 grams of prostate tissue was minced and co-cultured with 1–3 million normal, human donor marrow cells for 2–7 days. Marrow not co-cultured with tumorserved as a control. Target cells were collected and total RNA was analyzed for prostate-specific gene expression byReal Time RT-PCR. Fold differences in expression of the genes were analyzed, using TaqMan®, gene assays (Applied Biosystems) and were expressed in relation to the marrow control. Results: We have observed significant increases in gene expression in marrow cells co-cultured with prostate tumor cells (Gleason grades 6–9). Variable increases in expression were seen in 3 patient samples, as high as 7-fold for ERG, greater than 10-fold for ACPP and greater than 100-fold for STEAP, PART, TMPRSS2, PSCA and ETV1. Conclusions: These studies demonstrate that prostate specific genes are present in fresh human marrow cells after co-culture with tumor tissue. This establishes a base to begin evaluating the significance of microvesicle-mediated genetic transfer, mechanisms of transfer and therapeutic options for blocking or manipulating such transfer to influence the disease process. No significant financial relationships to disclose.
A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer
Authors: Joensuu T. K. , Joensuu G. , Nokisalmi P. , Reddy C. , Isola J. , Ruutu M. , Kouri M. , Kupelian P. , Hemminki A. 
Published: August 2020

e16079 Background: We estimated the safety and tolerability of 250 mg gefitinib q.d. given concurrently with three- dimensional conformal radiotherapy (3D-CRT) in patients with non-metastatic prostate cancer (PC). Methods: 42 patients with T2/T3N0M0 PC were treated in a single centre, non-randomized study (study code ZD1839/IL0118). PSA<20 and good performance status (WHO 0–1) were required. Adjuvant or neo-adjuvant hormonal treatments were not allowed. 250 mg gefitinib q.d. was started one week before and lasted for the duration of radiation therapy. 50.4 Gy (1.8 Gy/day) of 3D-CRT was administered to the tumor, prostate and seminal vesicles, followed by a 22 Gy booster (2 Gy/day) for a 72.4 Gy total dose. EGFR expression, presence of EGFRvIII and activated pEGFR were studied. Levels of serum TNF, IL-1 α and IL-6 were also evaluated. Results: Maximum tolerated dose was not reached in phase I (12 patients) and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication and 12 (28.6%) prematurely discontinued because of adverse events. Dose-limiting toxicities were recorded in 16 (38.1%) patients, the most common of which was grade 3–4 transaminase increase (6 patients). After median follow-up of 38 months nobody had died of PC. The estimated PSA-free survival rate at 4 years (Kaplan-Meier) was 97%, hormone-free survival 91% and overall survival 87%. These figures compared favourably with matched, non-randomized patients treated with radiation only. Data on biochemical analyses will be presented. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity in non-metastatic PC. A randomized study is being discussed for evaluating the efficacy of the approach. [Table: see text]
Sensitivity and specificity of osteopontin (OPN) versus prostate-specific antigen (PSA) in prostate carcinoma (PCa): A case- control study
Authors: Libener R. , Montefiore F. , Bonini F. , Ruggero L. , Maffezzini M. , Puntoni M. , Nanni L. , Paganuzzi M. , Puntoni R. , Betta P. 
Published: August 2020

e16082 Background: OPN is a secreted adhesive glycoprotein overexpressed in human cancers. A stimulatory effect of OPN on human PCa cells in vitro has been demonstrated. This study intends to determine if measuring serum OPN and PSA levels can provide informative markers for the detection of PCa. Methods: Serum total PSA using a chemiluminescent immunoassay system (Hybritech PSA, DxI Beckman Coulter, Inc.) and plasma OPN using an ELISA technique (R&D Systems, Inc.) were measured in 263 male subjects referred for diagnostic prostate biopsy, including 167 control patients with benign prostate pathology (mean age: 65.30; median age: 66; SD: 6.80; range 46–83) and 96 PCa patients (mean age: 66.80; median age: 68; SD: 7.90; range 47–86). Sensitivity and specificity were determined for each marker. The relationship between sensitivity and specificity was profiled by receiver operating characteristic (ROC) curves of OPN and PSA. Results: Both markers levels were higher in PCa patients (OPN 51.98 ng/ml, SD 32.64, range 5.9–169.54; PSA 12.91 ng/ml, SD 14.73, range 1.69–90) than in controls (OPN 49.93 ng/m, SD 27.78, range 4.15–146.34; PSA 8.04 ng/ml, SD 5.94, range 0.46–45), although the elevation was significant (p<0.001) for PSA but not for OPN (p=0.59). The increase of serum OPN level paralleled the increase of the tumour size, defined by the T stage, and was more striking for T ≥2 PCa than for T1 PCa. The increase of PSA, related to the tumour size, was less evident and was observed only in high stage (T3) tumours. The ROC curve showed that OPN was not a marker that enabled the discrimination between PCa and non-cancer patients. For PSA, a cut-off value of 4 ng/ml had a sensitivity of 93% with a specificity of 13%. A cut-off value of 5 ng/ml resulted with a sensitivity of 85% and specificity of 26%. Conclusions: OPN and PSA are not correlated and therefore their combined evaluation in a larger study group could provide a novel insight into the natural history of PCa. A follow-up of the patients involved is ongoing in order to assess a possible prognostic role of the two markers. (The study was funded by the Alessandria branch of the Italian League against Cancer through a grant from the Cassa di Risparmio di Alessandria Foundation) No significant financial relationships to disclose.
Protein profiling of tumor tissues by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discriminate between localized and metastatic renal cell carcinoma
Authors: Kamai T. , Tomosugi N. , Abe H. , Yoshida K. 
Published: August 2020

e16098 Background: We previously reported that mRNA of interferon-alpha receptor type 2 (IFNAR2) was upregulated in metastatic and IFN-a resistant renal cell carcinoma (RCC) in comparison to localized RCC or metastatic tumors with good response to IFN-a (BMC Cancer, 2007). We speculated potential different molecular mechanism between above two groups. Protein profiling using human tumor tissues may give insight into cellular pathways leading to carcinogenesis and metastasis in RCC. Methods: We examined mRNAs expression for IFNAR2 in paired tumor and non-tumor samples from the surgical specimens of Japanese patients with RCC using a real-time reverse transcription polymerase chain reaction. Then we selected representative five IFNAR2 upregulated clear cell carcinomas cases with metastatic tumor, five IFNAR2 upregulated metastatic sarcomatoid carcinomas, and five normal expression clear cell carcinomas with localized tumor. We investigated protein profiling in the tumor tissues of above three groups using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) coupled with IMAC-Cu chips. Results: For hierarchical clustering analysis, we used the 25 peaks which revealed significant differences in single-marker analysis in the range from 1,500 to 10,000 m/z. The heat map analysis based on the clustering distinguished completely metastatic tumors with IFNAR2 upregulated groups from localized tumors with IFNAR2 normal expression group. Furthermore, the heat map discriminated metastatic sarcomatoid carcinomas from metastatic clear cell carcinomas with a sensitivity of 100% and a specificity of 80%. Conclusions: SELDI-TOF MS profiling of tumor tissues can be applied to differentiate patients with three types of RCCs. Our findings may reflect different molecular mechanism between localized and metastatic carcinomas, and the different response to immunotherapy with IFN-α. This may shed light on the potential therapeutic strategy for IFN-α treatment. However, further investigation is required to verify the usefulness of this method in clinical practice. No significant financial relationships to disclose.
Characterization of lymphoid infiltrates in prostatectomy specimens post neoadjuvant hormonal therapy using quantitative immunofluorescence and RNA FISH
Authors: Donovan M. J. , Khan F. , Powell D. , Capodieci P. , Gleave M. , Taylor I. , Gomez-Navarro J. , Cordon-Cardo C. 
Published: August 2020

e16104 Background: Immunotherapy for advanced prostate cancer requires an understanding of the host response including lymphocyte subsets and cytokine expression. Using quantitative immunofluorescence (IF), image analysis and RNA FISH we examined a series of prostatectomy specimens from patients, ± neoadvjuvant hormonal therapy (NHT) and determined their baseline immune characteristics. Methods: CD4,8,25,45,68,69,86 and Foxp3 were evaluated by IF and IFNg with RNA FISH on prostatectomy specimens from 40 patients with T1c-T3 prostate cancer; 20 control and 20 post long-term NHT. Sections were analyzed with three multiplex IF assays, triplicate images acquired with spectral imaging, digitally masked and processed with IF image analysis software. IFNg RNA transcript localization was performed on all 40 patients using published protocols. Results: There was a predominance of CD8 in both control and NHT patients with a high but variable level of CD86 and 69 across the entire cohort, reflecting T cell activation. CD68 appeared reduced in NHT, but this change was not statistically significant. Number of Treg (CD4+/CD25+/Foxp3+) cells were similar between groups; however, in NHT an increased Treg population was associated with an elevated preoperative PSA compared with controls (p<0.05). IFNg transcript activity was low in the entire cohort and limited to tumor epithelial cells. Conclusions: The prominent CD8 expression and low level of IFNg in both control and NHT groups suggest an ongoing but not overly active immune response. Multiplex IF and in situ RNA FISH are useful tools for developing a disease phenotype and provide the necessary parameters for evaluating gene-protein expression especially in pharmacodynamic studies. [Table: see text]
Sequential and intermittent docetaxel (D) and imatinib (Im) in hormone-refractory prostate cancer patients (NYU 04–47)
Authors: Gómez-Pinillos A. , Ballard H. , Shelton G. , Reilly M. M. , Chachoua A. , Taneja S. , Ferrari A. C. 
Published: August 2020

e16108 Background: Platelet-derived growth factor is frequently expressed in advanced prostate cancer (PC) lesions where it supports PC cell growth and neo-angiogenesis. Im. is a PDGF inhibitor that blocks cell cycle in G1-S due to MEK/erk inhibition. D blocks cell cycle progression in G2-M. Sequential block of the cell cycle progression in G2-M followed by G1-S may increase anti-tumor responses. The phase II study dose of sequential D on day 1 and Im started 24–36h later given daily for 14 d was established in a previous phase I. Methods: Eligibility: at least 2 prior hormone manipulations and up to one prior chemotherapy, PSA>5ng/ml, ECOG PS 0–2. Treatment schedule: D 70mg/m2 day 1 followed 24–36 hours later by Im 600mg PO daily × 14 days. Cycles were repeated every 21d until toxicity or progression. Pegfilgrastim was given each cycle for neutropenia prevention. A two steps design was planned to assess activity (PSA decline >50% and/or measurable or symptomatic response) and tolerance including interim analysis to determine if 37 patients (pts) should be enrolled. Results: Of 15 pts enrolled, 13 had metastasis and 5(33%) received prior chemotherapy. There were 98 cycles of trial therapy administered and 9 events (PSA or bone progression) registered at the time of analysis. Median baseline PSA 73,5ng/ml (2.1–1954.3). Median follow-up estimated by inverse Kaplan Meier: 308 days (CI95%, 133–482). Median of cycles administrated 6 (1–12). PSA decline >50% observed in 7/15pts (46.67%) of which 3 was >80% (20%). PSA decline <50%, observed in 6/15(40%). 2/15(15.3%) were non-responders. Pain scores improved in all symptomatic pts. Median duration of response was 162 days (42- 281). Estimated median progression free survival by Kaplan-Meier was 155 days (CI95%, 80–339). Toxicity: there was G1–2 fatigue, anorexia, weight change in 66% pts; nausea, vomiting, taste changes in 66% pts, anemia in 46% and neuropathy in 46% pts. G3 fatigue in 2 pts, neuropathy and CHF in 1 pt. No G4 toxicities were observed. Conclusions: Sequential and intermittent D every 21 days and Im for 14 days is tolerable and active by PSA decline and symptomatic improvement. Compared to previous report with weekly D and continuous Im, this alternative schedule appears to have similar activity with better tolerance. [Table: see text]
Prognostic role of somatostatin receptor subtypes in human prostate cancer
Authors: Gernone A. , Pagliarulo V. , Trabucco S. 
Published: August 2020

e16120 Background: Neuroendocrine differentiation (NED) in prostate carcinoma (PC) is frequently detected by immunohistochemistry as single cells in conventional adenocarcinoma. NED of PC correlates with poor prognosis and tumor progression during androgen-deprivation therapy. The aim of our study was to correlate the expression of somatostatin receptor (SSTR) 1, 2, 3, 4, 5 subtypes in primary PC with NED pattern and Overall Survival (OS). Methods. PC tissues were reviewed from 100 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2002 to 2007. 24 samples expressed hystologically chromogranin A (CgA), a marker of NED expression. Patient characteristics included: median age 68 years (range 45–83), median baseline PSA: 70 ng/ml (range 0.3–200), median ECOG Performance Status: 1 (range 0–2), Gleason score ≥ 7, medium serum level of CgA was 56.2 nmol/L (range 0.5–120). Results: The expression of SSTR subtypes (1, 2, 3, 4, 5) were investigated and our data identified four histological features. SSTR1 was expressed in 4/24 samples, SSTR 5 was detected in 2/24 samples, both SSTR1 and SSTR5 were found in 6/24 samples. OS at last follow up on July 2008 was 60%. SSTR 1–5 were undetectable in 12/24 pts with more aggressive clinical course and the OS was < 10%. The PSA and CgA levels were not correlated with clinical outcome. SSTR subtypes 2, 3 an 4 were not expressed in all 24 samples. Conclusions: SSTRs expression significantly correlated with OS. The absence of SSTR 1 and 5 in more aggressive disease could represent a growth advantage in NED prostate cancer. SSTRs and somatostatin analogs are potential targets for prostate cancer treatment. No significant financial relationships to disclose.