bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunodetection of androgen and estrogen a,b receptors in human urinary bladder cancer
Authors: Gómez Pinillos A. , Bueno Serrano G. , Sacristán López S. , García González R. , Varona Crespo C. , Fernández Fernández E. , Moyano Jato A. , Arenas Jiménez M. , Toledo Lobo M. 
Published: March 2020

15616 Background: Bladder cancer predominates in males. Loss of androgen receptor (AR) has been associated with invasive and undifferentiated tumors but little is known about the role of hormonal receptors in this type of cancer. Methods: We evaluated samples from 41 nonconsecutive patients treated for bladder transitional cell carcinoma between 2001–2003. Immunohistochemistry was performed using anti-AR and anti-ER a,b antibodies on paraffin-embedded tumors from transurethral resections, nuclear expression was assessed. Western blotting for AR and pAKT were performed in 22 transurethral resections from nonconsecutive bladder cancer patients treated between 2004–2006. Chi-square and U Mann-Witney tests were performed. Results: Immunohistochemistry study: the male/female ratio was 9/1; 61% were noninvasive tumors (pTa, is,1) and 32% were invasive (pT2,3); 22% were G1 and 75% were G2,3. 95% were AR(+), 40% ERa(+) and 94% ERb(+). Significant differences in AR expression were observed between G1 78% and G2,3 tumors 100%, with a high grade tumor prevalence in the AR(+) tumors 81.6% p=0.046. No differences between ERa,b and differentiation were found. G2,3 tumors were predominantly ERb(+). AR was found in 92% noninvasive and in 100% invasive tumors p=0.53. No significant differences were found between invasiveness and ERa,b. Noninvasive tumors showed higher ERa,b expresión (54%, 95% respectively) than invasive tumors (20%, 91% respectively). Western blotting group: 54.5% were primary tumors and 45.5% were recidives. The noninvasive/invasive rate was 59/32%, the G1/G2,3 rate was 4.5/95.5%. 112, 250 and 160 kDa bands were found. AR/pAKT rate was 86.4/100%. 100% of invasive tumors and 86% G2,3 tumors were AR(+). No differences between pAKT, invasiveness, differentiation or AR expression were observed but recidivated tumors had a slight higher median expression level. Conclusions: AR is positively related to tumor grade and might be involved in bladder cancer progression. The profile of AR bands suggest covalent modifications, due to ubiquitin-mediated degradation or to activation mechanisms mediated by SUMO. Nuclear AR and the absence of bands under 90kDa suggest that activated protein is present in bladder cancer. pAKT/AR inhibitors could play a role for bladder cancer therapy. No significant financial relationships to disclose.
Is the blood-brain barrier relevant in metastatic germ cell tumors?
Authors: Azar J. M. , Einhorn L. H. , Schneider B. P. 
Published: March 2020

15618 Background: Metastatic germ cell tumors (GCT) are highly curable. Central Nervous System (CNS) recurrence can terminate a complete remission in other chemosensitive tumors such as small cell lung cancer due to the blood brain barrier (BBB). We document that the BBB can also be relevant in GCTs despite dramatic chemosensitivity. Methods: We present five cases of CNS only relapse in GCTs. None of these five patients had CNS metastases at the start of chemotherapy. Results: We have identified five unique patients from our large series of metastatic testicular cancer patients treated with chemotherapy. These patients were rendered free of disease with cisplatin- based chemotherapy only to relapse in the brain alone ( Table 1 ). This included one patient with good risk disease by the International Germ Cell Collaborative Group staging system (Patient #5). All patients had pulmonary metastases at diagnosis and a component of embryonal carcinoma. Three patients are alive without evidence of disease (NED) at 19, 32 and 8 months. One patient died of his disease (DOD) and one patient is alive with disease (AWD). Conclusion: The blood brain barrier is relevant in metastatic testicular cancer. [Table: see text] No significant financial relationships to disclose.
The value of PET-CT (positron emission tomography) in the treatment of metastatic renal cell carcinoma with sorafenib
Authors: Stierner U. , Boijsen M. , Suurküla M. , Lundstam S. 
Published: March 2020

15621 Background: Sorafenib is a new potent multikinase inhibitor directed against both tumour proliferation and angiogenesis. Clinical benefit has been shown in 75% of patients with metastatic renal cell carcinoma. The aim of this study was to evaluate this new treatment with PET-CT with fluorodeoxyglucose (FDG), since the use of only CT measurements has been questioned. Methods: 10 patients (8 male, 2 female, 49–72 years) with metastatic renal cell carcinoma (9 clear cell, 1 chromophobe). All had progressive disease (8 after interferon). Sorafenib 400 mg b.i.d was given orally. FDG-PET-CT scan was performed from head-proximal thigh before treatment and after one month. Up to 6 target lesions in each patient were studied. The sum of the largest diameters was calculated from CT images for each patient. To evaluate the glucose uptake, a region of interest (roi) was designed for each leasion on the initial PET on the transverse section where the lesion appeared to be largest and/or most intense. Using the same roi for subsequent examinations the mean glucose uptake/mean cerebellar uptake was calculated. For each patient the mean change from baseline was calculated. Results: After one month of treatment the sum of tumour diameters measured by CT was mean 85% (53–110%) of the initial value. Measured by PET the mean glucose uptake at one month was mean 73% (29–100%) of the initial value. Seven patients had skeletal lesions. These were often difficult to measure on CT and only small changes were detected. Using PET the mean uptake in skeletal lesions was 77% (62–104%) at one month. Conclusions: Early effects of sorafenib treatment in metastatic renal cell carcinoma can be detected and quantified by PET-CT. Especially in skeletal lesions PET-CT exhibits considerable benefits over CT by visualizing responses otherwise missed. Future studies will reveal if a decrease in tumour glucose uptake at one month correlates with the more clinically relevant endpoints PFS and OS. [Table: see text]
Retrospective analysis of patients with nonseminomatous testicular germ cell tumor and resection of postchemotherapy residual lung and mediastinal masses
Authors: Assad D. X. , Dienstmann R. , Metzger Filho O. , Rodrigues A. N. , Olmedo D. B. , Small I. A. , Herchenhorn D. 
Published: March 2020

15633 Background: Treatment of nonseminomatous testicular germ cell tumor (NSGCT) involves surgery of postchemotherapy (PC) residual masses. The resection of immature teratoma or viable cancer prolongs disease-free and overall survival. Discordance of histology among different sites of residual masses has been reported to occur in one-third of the patients and therefore, all identified masses must be removed. This study aims to evaluate the histology of residual masses in patients submitted to thoracic surgery for NSGCT and estimate time to progression after surgery and overall survival. Methods: Retrospective analysis of all patients with NSGCT and PC residual lung and mediastinal masses treated at the Brazilian National Cancer Institute between 1997 and 2006. Results: Of the 16 patients included, 10 patients had residual lung masses, 5 had both lung and mediastinal masses and 1 had mediastinal mass. Median age at diagnosis was 26.5 years. Embryonal carcinoma plus yolk sac tumor was the most frequent testicular histology (31%). Nine (56%) had stage IIIC disease and 7 (44%) were high-risk at the IGCCCG score. All patients received platinum-based chemotherapy (one had platinum-refractory disease). Of the 15 patients who had lung masses, 8 had bilateral disease. Histology of residual lung masses was necrosis in 8 patients (53%) and teratoma in 7 (47%). There was 100% concordance in the histology of bilateral lung masses. Ten patients (62%) had concomitant retroperitoneal masses. In only 3 of these patients (33%) there was concordance between retroperitoneal and lung histology. Median follow-up after surgery was 21.5 months. Five of the 16 patients (31%) had disease progression. One patient died (this patient had platinum-refractory disease). Median time to progression was 10 months and median overall survival was not reached. Conclusions: These data confirmed the small concordance between the histology of PC residual masses in the lung/ mediastinum and retroperitonium in NSGCT. There was concordance in the histology of bilateral lung masses. These findings suggest that all sites of residual masses should be resected and the presence of necrosis in residual lung masses indicates no need for contralateral resection. No significant financial relationships to disclose.
Intermittent androgen deprivation therapy (IADT) for patients with non-metastatic prostate cancer: A retrospective review
Authors: So-Rosillo R. , Small E. J. , Weinberg V. 
Published: March 2020

15635 Background: IADT is a therapeutic option frequently utilized in men with progressive non-castrate prostate cancer (PCa) which, compared to continuous ADT, may result in an improvement in quality of life while potentially prolonging time to androgen independence (AI). Methods: The records of 43 consecutive men with non-metastatic progressive non-castrate PCa treated with IADT were analyzed. 21 men had received no prior primary treatment (tx), and 22 had developed recurrent disease after previous local therapy. Therapy for this cohort of patients (pts) consisted of combined androgen blockade for 32 pts and a leutenizing hormone-releasing hormone agonist alone for 11. Pts were allowed to come off androgen deprivation (AD) when (a) PSA became undetectable, (b) after 9 to 12 months (mos) of receiving AD, (c) or per patient request. AD was re-initiated when (a) serum PSA reached 50% or greater of the pre-tx level, (b) at physician discretion, or (c) at patient's request. A tx cycle was defined as the number of months on tx plus the number of months off tx until the reinstitution of AD. Progressive disease and AI were defined by consensus criteria (climbing PSA despite AD). Results: Follow up ranged from 18 to 153 mos (median 68.2 mos) from the start of tx. Pts received from 1 to 10 cycles (median 4), with a median cycle length of 19 mos. The median pre-tx PSA value was 8.9, and the median nadir serum PSA level with ADT was 0.09 and was reached within an average of 6.4 mos (range 2–25) after beginning tx. Pts spent an average of 50.7% of time on hormones and 49.3% off hormones. Eleven pts developed AI progressive disease, with a median time to progression of 47 mos. When examining for potential characteristics that contributed to AI, such as duration of ADT, PSA at start of therapy, nadir PSA, stage, or Gleason score, no consistent patterns of failure emerged. Conclusions: IADT appears to be a viable tx option for men with non-metastatic progressive non-castrate PCa, resulting in prolonged duration of response. However, with a median follow up of nearly 6 years, AI still develops in over a quarter of pts, at a median of 47 months from starting ADT. No significant financial relationships to disclose.
Efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin (Ox) in pre-treated advanced epithelial ovarian cancer (EOC) in relation to BRCA status
Authors: Nicoletto M. O. , Donach M. E. , Borgato L. , Artioli G. , Zovato S. , Barile C. , Bertorelle R. , Cartei G. 
Published: March 2020

16006 Background: The mechanism of action of PLD+Ox suggests that and carriers of BRCA mutations might have better survival compared to sporadic ovarian cancer even when pre-treated in advanced EOC. Methods: Inclusion criteria: Performance Status<=2, relapse or progression after 1–3 lines of therapy; <=4 prior antiblastic drugs; life expectancy >3 months; LVEF >50%, informed consent. Treatment consisted of 1 hr infusion of PLD 30–35 mg/m2 on day 1 and 70 mg/m2 of Ox in 2 hrs on day 2 for 8 cycles, then 2 cycles of PLD alone. Clinical response was evaluated by CT scan every 3 cycles. Primary endpoints were overall survival and its correlation with BRCA mutations and p53. Results: From June 2000, 63 pre-treated pts with advanced EOC were enrolled. Median age = 62 yrs, range 41–83, (18pts >70 yrs). 17 had known germline BRCA1/2 mutations (10pts) or family history of ovarian cancer (4pts). In this BRCA/high-risk population 15 pts were evaluable for response with ORR=93.3% (8 CR, 6 PR>50%, 1 SD). 139 courses were administered (median = 10 courses/pt). There was 1 episode of G3 toxicity: mucositis; G1–2 toxicity was gastrointestinal (16 episodes), mucositis (11 episodes), neutropenia (9 episodes). Median LVEF showed no significant changes during treatment. There is no clear correlation between OS and amount of Platinum/Taxol administered previously. p53 was analyzed for expression and mutations. Mutations were sought in exons 5, 6, 7 and 8. 5/6 CR evaluable for p53 showed overexpression. p53 overexpression was seen in 9/11 evaluable pts; of these 4/9 also had p53 mutations. 3/4 of these patients obtained a complete response. Median survival from 1st cycle has not been reached; mean survival is 63.6 months vs 24.7 for sporadic EOC (p<.001). Presently 15/17 are alive. The 5-yr survival after first course of therapy is estimated at 82%. BRCA/high-risk patients in PLD-Ox therapy also fared better than counterparts from an historical population (OS from diagnosis 179.4 vs 141.1 months, p=.005). Conclusions: PLD+Ox is well tolerated and highly effective in BRCA/high-risk patients and in p53 positive/mutated pts in this population. This therapy offers low toxicity providing good quality of life. No significant financial relationships to disclose.
Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)
Authors: Prat A. , Del Campo J. , Peralta S. , Cedres S. , Perez A. , Gil A. , Martinez-Palones J. , Garcia A. , Baselga J. 
Published: March 2020

16007 Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. >65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (>35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p< .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p< .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted. No significant financial relationships to disclose.
Serum YKL-40 levels are usuful diagnostic tumor markers for adenocarcinoma of the uterine cervix
Authors: Mitsuhashi A. , Usui H. , Matsui H. , Tate S. , Unno Y. , Hirashiki K. , Shozu M. 
Published: March 2020

16008 Background: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth factor, play a role in angiogenesis, or prevent apoptosis. The current study examined serum YKL-40 levels in patients with adenocarcinoma of the cervix to determine if it is a serum marker. Methods: The serum YKL-40 level was assayed by enzyme-linked immunosorbent assay in 24 patients with benign gynecologic disease, in 104 patients with squamous cell carcinonma , in 37 patietns with adenocarcinoma, and in 45 healthy controls, Serum squamous cell carcinoma antigen (SCC) and CA125 and CA19–9 values were obtained. Results: The serum YKL-40 level was higher in patients with cervical carcinoma than in the healthy controls (p<0.0001). YKL-40 concentrations increased significantly in patients with squamous cell carcinoma and in those with adenocarcinoma (vs. normal control: p<0.0001 and p<0.0001, respectively). Judging from the receiver operating curves (ROC), the serum YKL-40 was more sensitive than other serum markers at identifying adenocarcinoma. In squamous cell carcinoma, this ability of serum YKL-40 was equal to that of SCC. YKL-40 was elevated in 68.4% of patients with stage I adenocarcinoma. The pretherapeutic serum level of YKL-40 correlated significantly with the International Federation of Gynecology and Obstetrics advanced stage in patients with adenocarcinoma of the cervix. Furthermore, the pretherapeutic serum level of YKL-40 correlated with disease persistence or recurrence. Conclusions: The serum YKL-40 level has potential usefulness as a diagnostic marker of adenocarcinoma of the cervix. [Table: see text] No significant financial relationships to disclose.
Safety and efficacy of pegfilgrastim administration on the same day as myelosuppressive chemotherapy (CT) in women with ovarian or primary peritoneal cancer
Authors: Schuman S. I. , Lambrou N. , Robson K. , Glück S. , Myriounis N. , Pearson J. , Alvarez E. , Crisp M. P. , Twiggs L. B. , Lucci J. A. 
Published: March 2020

16009 Background: According to prescribing information, pegfilgrastim should not be administered within 14 days prior to, or within 24 hours after, the administration of cytotoxic CT. However, little data exist to support this recommendation. The purpose of the current study is to determine the safety and efficacy of administering pegfilgrastim on the same day as myelosuppressive CT in patients with ovarian or primary peritoneal carcinoma. Methods: A retrospective review was conducted of all ovarian and primary peritoneal cancer patients that received prophylactic pegfilgrastim on the same day as CT from May 2003 to June 2006. Results: Forty-six patients (mean age: 57, range: 21–82) were treated for the following malignancies: 35 (76%) epithelial ovarian, 6 (13%) primary peritoneal, and 5 (11.0%) ovarian germ cell or stromal cell carcinoma. Twenty-six patients (56%) had primary cancers and 20 (44 %) had recurrent disease. All patients met the ASCO or NCCN recommendations of using colony-stimulating factors for prophylaxis against febrile neutropenia (FN) (Risk of FN > 20%). A total of 269 cycles of CT were administered including 125 cycles (46.5%) docetaxel + carboplatin, 39 cycles (14.5%) gemcitabine + platinum, 30 cycles (11.1%) intravenous paclitaxel + carboplatin, 28 cycles (10.4%) liposomal doxorubicin, 19 cycles (7.1%) paclitaxel + intraperitoneal platinum, 6 cycles (2.2%) docetaxel, 6 cycles (2.2%) liposomal doxorubicin + cisplatin, 5 cycles (2%) bleomycin + etoposide + cisplatin, 4 cycles (1.5%) topotecan, 3 cycles (1.1%) of paclitaxel, 2 cycles (0.7%) vincristine + actinomycin-D + cyclophosphamide, and 2 cycles (0.7%) docetaxel + gemcitabine. All patients received pegfilgrastim within one hour of the completion of CT administration. Grade 1 or 2 neutropenia developed in 10 cycles (3.7%) out of the 269 cycles, mean absolute neutrophil count = 4926 (range, 1293 -24300). No patients had FN episodes, hospitalizations or antibiotic use secondary to neutropenia, or dose-reductions and CT delays due to neutropenia. Conclusions: Administration of pegfilgrastim on the same day as CT in ovarian and primary peritoneal cancer patients is more convenient to the patient and appears safe and effective. No significant financial relationships to disclose.
Phase I/II study to evaluate the optimum dose of pegylated-interferon (PEG INTRON) in patients with platinum-resistant ovarian cancer
Authors: Soliman P. T. , Gano J. B. , Levenback C. F. , Kavanagh J. , Gershenson D. M. , Wolf J. K. 
Published: March 2020

16010 Background: Intraperitoneal interferon therapy has been shown to have response rates as high as 45% in patients with recurrent ovarian cancer. Continued exposure has also been associated with the effectiveness of interferon treatment. The purpose of this study was evaluate the optimum dose and toxicity profile of PEG INTRON given subcutaneously (SC) on a weekly schedule to women with platinum-resistant ovarian cancer. Methods: Women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer were eligible. Those whose tumors tested positive for IL-8, bFGF, or VEGF were randomized to three PEG INTRON treatment doses, 1.0, 1.25, or 1.5 micrograms/kg/wk SC for a total of 4 weekly injections per cycle. Re-evaluation for tumor response by imaging, physical exam and CA-125 was performed every 2 -3 cycles (8 - 12 weeks). Up to 12 cycles of treatment was allowed. Treatment was continued until progression of disease or unacceptable toxicity. Results: Thirty patients were enrolled, only 17 received treatment; 11 tested negative, 1 refused testing, 1 tested positive but refused treatment. Median age was 56 years (35–73). Of those treated, 94% (16/17) had a performance status of 0. All were heavily pretreated (3–8 prior chemo regimens). One patient received 9 cycles (1.25 micrograms/kg, total dose = 80 mcg) with stable disease. In the remaining 16 patients, 14 (75%) were taken off study due to disease progression; 3 after completing 2 treatment cycles and 11 after <2 treatment cycles. Four patients (24%) discontinued treatment because of toxicity. Two episodes of grade 4 fatigue were reported. Other grade 3 toxicities included visual changes, pain, anemia, neutropenia, depression, myalgia, and nausea/vomiting. Conclusions: There were no clinical responses to weekly PEG INTRON in this patient population. In addition, the regimen was difficult to tolerate. Further investigation into the dose and delivery of PEG INTRON is needed to determine the safety and efficacy of interferon treatment in patients with reuccurent ovarian cancer. No significant financial relationships to disclose.