bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma
Authors: Tsimafeyeu V. I. , Madzhuga A. , Demidov L. 
Published: August 2020

e16134 Background: In experimental systems, interference with coagulation can affect tumor biology. We suggested that abnormal coagulation could be a negative predictor for response to immunotherapy and survival among patients with metastatic renal cell carcinoma (MRCC). Methods: To address this issue, retrospective analysis of 289 previously untreated MRCC patients entering on institutional review board-approved clinical trials was conducted between 2003 and 2006. In addition, two groups of MRCC patients with (n = 28) or without (n = 28) hypercoagulability were compared in a case-control study. Baseline and treatment characteristics were well balanced. Results: Hypercoagulability was present at treatment start in 40% of patients. Median baseline fibrinogen was 6.2 mg/dl. Serious disorders were found in 68% of patients. Abnormal coagulation was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0–1 (p = 0.001). Patients with high extent of hypercoagulability had significantly higher number of metastatic sites (p = 0.02). On univariate analysis, patients with hypercoagulability had significantly shorter overall survival than patients with normal coagulation; median survivals of 8.9 and 16.3, respectively (p = 0.001). Short survival and low response rate also were significantly associated with hypercoagulability in a case-control study. Median cancer-specific survival was 8.2 months and 14.6 months, respectively (p = 0.0011). Disease control rate (overall response + stable disease) was significantly higher in patients with normal coagulation: 71.4 versus 42.9% (p = 0.003). We did not reveal VTE-related deaths. Conclusions: Hypercoagulability disorders were found to be prognostic factor for response rate to systemic therapy and survival in patients with MRCC. No significant financial relationships to disclose.
MR-based biomarkers in the diagnosis and the evaluation of the therapeutic response to radiotherapy (ETRR) in prostatic carcinoma (PCa): Implementation of clinical and experimental approaches
Authors: Crehange G. , Walker P. M. , Parfait S. , Maingon P. , Cochet A. , Brunotte F. , Tizon X. , Provent P. , Duchamp O. 
Published: August 2020

e16136 Background: ETRR in PCa remains a challenging task. New biomarkers in the form of metabolites, detected with Proton Magnetic Resonance Spectroscopy (1H-MRS), and quantitative Apparent Diffusion Coefficient (ADC), determined with Diffusion-Weighted Magnetic Resonance Imaging, could be of value in the ETRR for PCa. Methods: Twenty-one men with biopsy proven localized PCa were examined before external radiotherapy. 3D-1H-MRS was performed at 3.0T without endorectal coils. The delivered radiotherapy dose was 78 Gy in 39 fractions with 6 MV photons. MR follow-up examinations up to 36 months post-radiotherapy were performed. For the pre-clinical study, healthy rat prostate was studied in 3 nude rats. PC3-MM2 and PAC-120 tumors were subcutaneously (SC) and orthotopically (OT) xenografted in 5 nude rats, respectively. Radiotherapy anti-tumor efficacy administered as HDR-brachytherapy (SC) or X6 external beam irradiation (OT) delivering 10 Gy/5 fractions was evaluated. 1H-MRS was performed at 4.7 T using SVS. Results: Twelve men received the 3-month examination, 8 patients are at 6-months, 4 are at 9 months and 1 has been followed for 1 year. At baseline, healthy prostate shows a low Choline (Cho)/Citrate ratio, whereas the presence of cancer considerably increases this ratio. At 3 months, we observed metabolic atrophy except for Cho. Although, higher ADC values are normally found in peripheral zone than in central gland, these differences disappear after radiotherapy. In healthy rat prostate high levels of Cho without citrate were noted. Cho and free lipids were detected in PC3-MM2 and PAC120 SC-grafted tumors, with a higher Cho content in PC3-MM2. Radiotherapy induced significant antitumor activity in PC3-MM2 (SC) (T/C% = 38%) and OT (ILS% = 58%) tumors, but was not efficient in PAC120 SC-grafted tumors (T/C% = 90%). Radiotherapy slightly modified Cho content 4 days after the end of treatment but no modification on overall metabolic profile was observed before, during and after radiotherapy. Conclusions: Combined ADC and Cho are powerful biomarkers for the detection of PCa in men and could be useful for ETRR.The use of Cho in ETRR for PCa in rats appears to be promising. No significant financial relationships to disclose.
Elective open nephron-sparing surgery for renal masses: Single-center experience with 223 consecutive patients
Authors: Francesca F. , Pomara G. , Campo G. , Casale P. 
Published: August 2020

e16139 Background: To present our experience with elective, open, nephron-sparing surgery for renal masses in a contemporary, consecutive series. Methods: In this retrospective study, records of all patients who underwent elective nephron-sparing surgery (E-NSS) between March 1997 and December 2007 at our institution were reviewed. The preoperative workup included laboratory analysis, renal ultrasonography and abdominal computed tomography. The histological findings, complications, and oncologic outcome were studied. Results: A total of 231 E-NSS were performed in 223 patients (82 females,141males; mean age 64 years). 62 “hot ischemia” procedures and 169 “cold ischemia”. The mean tumor size was 4.6 cm (1.1–12cm). 52 patients presented renal masses > 4cm. Renal cell carcinoma was present in 177 patients (76.6%), benign renal masses were diagnosed in in 54 pazienti (23.3%): angiomyolipoma (35%), oncocytoma (40%), complicated cyst (25%). Worthy of note among these 54 patients, pre-operative diagnosis was present in 12 patients. Moreover, 17 benign lesions (31%) were > 4 cm. Complication rate was 5.3% (12 pts): splenectomy (2.2%), nephrectomy because of postoperative bleeding (0.8%), urinary fistulas (0.8%). After a median follow-up of 84 months (range 5 to 120), no patient had developed local recurrence, 19 (8.9%) died for other causes, 2 (0.9%) died for other tumor. Conclusions: The results of this contemporary, monocenter experience underline the role of open, elective, nephron-sparing surgery for patients with renal masses, confirming good results even for renal masses > 4cm. These conclusions are particularly important considering that benign histologic findings were present in almost one forth of patients. No significant financial relationships to disclose.
Detection of prostate cancer recurrence using an ultrasensitive nanoparticle-based PSA assay
Authors: Storhoff J. , Lubben T. , Lefebvre P. , Holzman T. 
Published: August 2020

e16146 Approximately 400,000 men are diagnosed each year with prostate cancer worldwide, and many of those patients undergo radical prostatectomy in an attempt to cure the disease. Although prostatectomy is effective for a majority of patients, approximately 15 to 40 % will experience prostate cancer recurrence within 5 years, and a majority of those patients will die from the disease (JAMA. 2008;299:2760-2769). Currently, prostate cancer recurrence is determined by monitoring prostate specific antigen (PSA) levels in patients following treatment, and those patients whose PSA levels rise above the clinical cutoff of 200 pg/mL PSA are defined as having recurrent prostate cancer. For those that do recur and have high PSA doubling times, early salvage radiotherapy confers a significant increase in prostate cancer specific survival (1). We have developed an ultrasensitive assay that measures PSA levels with a limit of detection of 0.5 pg/mL PSA with a CV of less than 20 % at 2 pg/mL. This assay utilizes functionalized gold nanoparticles to label PSA targets captured onto antibody coated glass substrates. The amount of PSA is quantified through silver enhancement of the functionalized gold. In this presentation, we describe the application of this technology in monitoring PSA levels in patients that are approximately 400 fold below the current clinical cutoff as a means of diagnosing prostate cancer recurrence at a much earlier timepoint than current assays. [Table: see text]
Cytokine changes in castrate metastatic prostate cancer (CPMC) patients (pts) treated with ipilimumab (Ipi)
Authors: Yuan J. , Orlandi F. , Jefferson M. , Li H. , Gallardo H. , Ku G. , Wolchok J. , Scher H. , Allison J. , Slovin S. F. 
Published: August 2020

e16149 Background: Ipilimumab (Ipi) is a human IgG1 monoclonal antibody that blocks the inhibitory action of the checkpoint molecule CTLA-4. Recent data [Proc Amer Soc Clin Onc, Abstr#5004, 2008] from castrate metastatic PC pts suggested that Ipi was active but was associated with grade 3 autoimmune adverse events (AEs), such as colitis, hepatitis, hypophysitis or rash, which required high dose steroids. We studied pts who were treated on a clinical trial with Ipi 10 mg/kg alone or with radiation to a single site in bone to determine whether there was any correlation between serum cytokine levels and autoimmune AEs. Methods: Thirteen pts were treated, of whom 10 had sufficient specimens for analysis. Of the 10 pts, 8 had ≥1 AE during treatment. Pts were stratified by ascertainment of clinical benefit (CB) vs. no clinical benefit (NCB) based on time-to-PSA-baseline relapse (TTBR) and also by toxicity (tox) using standard NCI tox criteria. TTBR was defined as time from study entry until the time when a PSA measurement reached or exceeded the baseline value. Pts with a TTBR greater than the median value were judged to have CB; those with a TTBR less than the median value had NCB. Pts with grade (gd) 0/1/2 tox were termed “low tox” while those with gd 3/4 tox were “high tox”. Sera at serial time points were analyzed for interferon-gamma (IFN-γ), tumor necrosis factor α and interleukins (IL)-1b, 2, 4, 8, 10, 12, 13 with the Meso Scale Discovery Multiplex Assay (MSD, Gaithersburg, MD). Results: IFN-γ was the predominant cytokine produced in 4 of 5 pts with CB and AEs; it increased at week 4 or 7 after two doses of Ipi, then declined. Four of 5 pts with NCB had minimal IFN-γ production. There was no difference in IL-10 production between those with CB vs. NCB or high vs. low tox. However, there was a suggestion that the IFN-γ /IL-10 ratio may be increased in pts who had high tox and/or CB vs. pts with low tox and NCB. This awaits confirmation. Conclusions: While this experience with Ipi in PC is small, there may be differences between pts with CB vs. NCB and pts with low vs. high tox. Investigation of the immunophenotype of pts who remain in follow- up and continue to be enrolled is ongoing as well as the impact of prior chemotherapy on development of toxicities. [Table: see text]
Cost-effectiveness analysis of first-line treatment for metastatic renal cell carcinoma (mRCC) in Colombia (ONCOLGroup study)
Authors: Godoy J. , Cardona A. F. , Cáceres H. , Otero J. M. , Lujan M. , Lopera D. , Pacheco J. O. , Spath A. , Gis P. 
Published: August 2020

e16150 Background: Renal cell carcinoma has increased its incidence by 126% since 1950. A local study developed a complete economic evaluation of sunitinib versus IFN in first-line treatment of mRCC in Colombia, finding that sunitinib was more cost-useful and cost-effective. Methods: A Markov model was developed using 6-week cycles for evaluating the cost-effectiveness of four interventions (IFN, sunitinib, bevacizumab+IFN, sorafenib) approved as first-line treatment for mRCC in Colombia. The model used the third-party payer perspective and a 5-year time-line; it also presumed that all the patients (pts) continued with active treatment until progression when it became acceptable to continue with a second-line treatment or BSC. Overall survival (OS) and progression-free survival (PFS) curves of IFN were used as reference framework; they were obtained form a published clinical trial. The hazard ratios (HR) for PFS and OS were estimated for comparing new generation medicaments with IFN. The information about frequency of use and health service cost units consumed in Colombia was taken from a series of 24 pts treated in Manizales, Pereira, Medellín and Bogotá. Service costs were requested from an external consultant and corresponded to the average value billed by the EPSs, calculated from 33 sources of information which were representative of the country's market. The cost of the medicaments was obtained from LCLC. The costs and benefits were discounted annually at 3%. (all cost are presented in Colombian pesos Col$ 2008 with an exchange rate 1 USD = 1836.20 Col$). Results: Incremental analysis indicated a difference of 41.1 million Col$ in the average total cost of treatment when Sunitinib was compared to IFN; in contrast, comparing sorafenib and Bevacizumab+INF to sunitinib demonstrated that the average total cost was less for the sunitinib by 8.3 and 104.2 million Col$, respectively. Additionally, the ratios of incremental cost-effectiveness by life years (LY) gained demonstrated sunitinib's simple dominance over sorafenib and the combination of bevacizumab+IFN, and an average by LY gained of 100.5 million Col$ compared to IFN. Conclusions: Sunitinib is the most cost-effective option as first-line treatment for mRCC pts in Colombia. [Table: see text]
Maintenance GM-CSF in patients with castration-resistant prostate cancer (CRPC) who maximized their response to chemotherapy
Authors: Bitran J. D. , Tolzien K. , Lestingi T. M. , Nabhan C. 
Published: August 2020

e16155 Background: There is no standard treatment for CRPC patients (pts) who completed chemotherapy. Time to progression (TTP) ranges from 3–6 months after stopping chemotherapy. GM-CSF (GM) is an immune-based growth factor with reported activity in CRPC. We hypothesized that GM maintenance in pts who have maximized their response to chemotherapy could delay TTP or time to next treatment (TNT). Methods: Eligible pts were those with CRPC who completed 10–12 cycles of docetaxel (D) or mitoxantrone (M) chemotherapy without progression; or those who maximized their response to chemotherapy before completing 10–12 cycles. Maximum response was defined as a <10% change in PSA repeated on two occasions with stable disease (SD) radiographically. Enrolled pts received GM at 250 ug/m2 subcutaneously for 14 days followed by 14-days of rest. GM was continued until disease progression. Primary end point was the clinical benefit defined as the sum of partial response (PR), complete response (CR) and SD. Secondary end points included toxicity, TTP, and TNT. Results: To date, 12 pts out of planned 20 have been enrolled (9 were on D and 3 on M). Median age was 78 (66–96). Median PSA at enrollment was 56.5 (0.1–566). Only 1 pt had a Gleason score < 7. Median time from initial diagnosis to GM was 70 months. Median number of chemotherapy cycles prior to GM was 9 (6–12). Eight pts (66%) had visceral and bone disease. GM was well-tolerated with no drug-related grade 3 and/or 4 toxicities. Ten pts are evaluable (1 pt withdrew consent and another did not comply). Median GM cycles received so far was 3 (2–11). With a median follow up of 11 months (2–17), 3 pts demonstrated SD and 2 had PR for an overall clinical benefit of 50%. One pt remains on study at 7 months while the median response duration for the other 4 responding pts was 7 months. Four pts never received another treatment but the median TNT in other evaluable pts was 3 months. Conclusions: GM is safe, well tolerated, and has activity in CRPC after stopping chemotherapy. Combining chemotherapy with GM should be investigated in future studies. [Table: see text]
Postoperative radiotherapy for prostate cancer: Sooner or later?
Authors: Igdem S. , Abacioglu M. U. , Alço G. , Ibrahimov R. , Kefeli A. , Çetin I. , Turkan S. , Okkan S. 
Published: August 2020

e16157 Background: To report our experience with adjuvant or salvage radiotherapy for prostate cancer and to assess the tolerance of the patients. Methods: The charts of 139 men who received postoperative radiotherapy (RT) after radical prostatectomy (RP) between 1997–2007 in two institutions were retrospectively analyzed. Thirty-seven percent received adjuvant RT and 63% salvage RT. The median age was 65 years (range: 43–80). Pathologic Gleason score was 2–6 in 24%, 7 in 56%, and 8–10 in 20%. Seminal vesicle involvement was reported in 34%, positive surgical margins in 72%, lymph node involvement in 7%, capsular perforation in 61%, and perineural invasion in 73% of the patients. The median PSA level before RT was 0.29ng/ml (range: 0–19ng/mL). Median time from RP to RT was 3 months (range, 1–12 months) in the adjuvant setting, and 27 months (range, 2–96 months) in the salvage setting. Nineteen percent received radiation to the pelvis, 81% to the prostate bed only. The median dose to the prostatic bed was 66.6Gy (range: 60–76Gy). Before, during or after RT 49% received androgen deprivation for a median of 6 months (range, 3–48 months). Biochemical failure is defined as a post-RT PSA level >0.2ng/mL. Results: The median follow up time was 41 months (range, 12–133 months). At 4 years, for the entire cohort biochemical control, metastasis free survival, and overall survival was 68%, 92%, and 94%, respectively. Although there was a significant difference in favor of the adjuvantly treated group for biochemical control (81% vs 60%, p = 0.03) in univariate analysis, multivariate analysis demonstrated that higher preoperative PSA level (p = 0.02), and lymph node involvement (p = 0.02) predicted for a worse PSA outcome. No grade 3 acute gastrointestinal (GI) or genitourinary (GU) toxicity was reported during the treatment. At 4 years, 4% of patients had Grade 2 late GI toxicity, 0.7% had grade 3 late GI, and 0.7% brade 4 late GI toxicity, while 16% of patients reported late grade 2 GU, and 4% had late grade 3 GU toxicity. Conclusions: Our results suggest that adjuvant RT may offer a better biochemical outcome in patients who underwent radical prostatectomy for prostate cancer. Overall, the number of high grade toxicities for postoperative RT was low. Therefore it can safely be used in appropriate setting. No significant financial relationships to disclose.
Significance of the expression of thymidylate synthase in prostate cancer
Authors: Mizutani Y. , Li Y. , Shiraishi T. , Nakamura T. , Mikami K. , Okihara K. , Takaha N. , Ukimura O. , Kawauchi A. , Miki T. 
Published: August 2020

e16163 Background: Thymidylate synthase ( TS ) is an important enzyme in de novo DNA synthesis pathway. 5-Fluorouracil ( 5-FU ), an anticancer chemotherapeutic agent used clinically against a variety of cancers including prostate cancer, inhibits DNA synthesis by binding TS. In the present study, we examined TS expression in prostate cancer and investigated its prognostic significance. Methods: Fifty-two prostate cancer tissue specimens were obtained from patients who underwent radical prostatectomy for prostate cancer without neoadjuvant hormonal therapy. Forty-eight prostate cancer tissue specimens were also obtained from patients who underwent radical prostatectomy for prostate cancer with neoadjuvant hormonal therapy. We examined prostate cancer tissue and normal prostate tissue for TS expression by immunohistochemistry. Results: TS was expressed at higher levels in prostate cancer without neoadjuvant hormonal therapy, compared with normal prostate.TS expression in stage T3 prostate cancer was higher than that in stage T2 prostate cancer. In addition, the level of TS expression in Gleason score 7 or greater prostate cancer was higher than that in Gleason score less than 7 prostate cancer. Patients with prostate cancer with negative TS expression without neoadjuvant hormonal therapy had a longer postoperative recurrence-free rate than those with positive expression in the 5 year follow-up. In addition, patients with Gleason score less than 7 prostate cancer with negative TS expression had a much longer postoperative recurrence-free rate than those with positive expression in the 5-year follow-up. TS expression was significantly decreased in prostate cancer patients who received neoadjuvant hormonal therapy, especially stage T2 prostate cancer patients. Conclusions: The current study has demonstrated for the first time that TS expression may be a prognostic parameterr for prostate cancer patients undergoing radical prostatectomy. No significant financial relationships to disclose.
Stage I nonseminomatous germ cell tumors of the testis: Clinical outcome of 45 patients on a surveillance protocol after orchiectomy alone at a single institution in Japan
Authors: Kakimoto K. , Ono Y. , Meguro N. , Takezawa K. , Yoshida T. , Arai Y. , Usami M. 
Published: August 2020

e16165 Background: In Japan, risk-adapted treatment for patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) has been performed in very few institutions. This retrospective study was performed to evaluate histopathologic prognostic factors with stage I NSGCTT for whom careful follow-up with a surveillance protocol was possible at a single institution. Methods: We included 45 patients with a median age of 31 years (range 16 - 58) who were managed with a surveillance strategy after orchiectomy in our department between 1972 and 2006. Mean duration of follow-up was 8.1 years (range 1.4 –30). The patients were monitored at follow-up evaluation for tumor marker (AFP, beta-hCG) levels and by abdominal CT scan, chest x-ray, and physical examination. Primary testis tumor samples were assessed for prognostic factors including lymphatic and/or vascular (LV) invasion and pathological components such as the presence of embryonal carcinoma. Log-rank analyses were performed to identify prognostic factors. Results: All patients were alive and disease-free. Relapses occurred in 16 (35.6%) patients after a median follow-up of 5.7 months (range 3–45). In 11 patients (68.8 %), relapse was detected in the retroperitoneal lymph nodes. Two patients (12.5%) had metastases in the retroperitoneal lymph nodes and lungs, two patients (12.5%) had metastases in the lungs alone, and one patient (6.2%) had metastases in the retroperitoneal lymph nodes, lungs, and brain. LV invasion was identified in 17 patients, 53% of whom had relapsed, and relapse was found in 25% of 28 patients without LV invasion (p<0.01). Of 31 patients with an embryonal carcinoma component, 13 patients (42%) developed metastases, whereas 21% of those without an embryonal carcinoma component developed metastases (p=0.04). After chemotherapy and/or surgical treatment for relapse, the 5-year overall survival rate was 100%. Conclusions: As in previous reports, the presence of an embryonal carcinoma component and LV invasion appeared to be factors suggesting a high likelihood of relapse. The surveillance protocol described here is a reliable strategy for stage I NSGCTT patients if careful long-term follow-up is possible. No significant financial relationships to disclose.