bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of hormonal receptor status in tissue from prostate cancer that developed 26 years after bilateral orchiectomy and following 41 years of estrogen therapy
Authors: Miksad R. A. , Bubley G. , Church P. , Cooper A. , Rofsky N. , Kaplan I. , Sanda M. 
Published: March 2020

14610 Background: The development of prostate cancer in the absence of normal male testosterone levels and in the presence of elevated estrogen levels is rare and poorly understood. Methods: The androgen, estrogen and progesterone receptors were evaluated in prostate cancer tissue from a 60-year-old, long-term transgender woman. Her serum hormone levels were assessed and the prostate specific antigen (PSA) level was followed during hormonal and radiation treatment. This patient began estrogen therapy at age 19 and underwent bilateral orchiectomy at age 34 during gender re-assignment surgery. Work-up for gross hematuria revealed a Gleason 8, locally advanced prostate cancer. Results: The tumor showed abundant staining for androgen receptors (AR), with a nuclear pattern consistent with hormone refractory prostate cancer. The tumor did not stain for estrogen receptors (ER) or progesterone receptors (PR). Compared to reference values for men, this transgender woman had low serum testosterone (44 ng/dl) and free testosterone (0.9 pg/mL) levels and elevated estradiol (53 pg/mL) and estrone (377 pg/mL) levels. Prior to the initiation of radiation, treatment with bicalutamide and dutasteride reduced her PSA from 240 ng/ml to 77 ng/ml at week 6 (see Table). After treatment with external beam radiation her PSA fell to 4.6 ng/mL. At week 24, her PSA was 0.8 ng/mL. Conclusions: This high-grade, locally advanced prostate cancer in a transgender woman represents the longest reported duration of a castrate state preceding the development of prostate cancer, exceeding prior reports by several decades. The AR positive and ER/PR negative status of this tumor in the setting of low testosterone and elevated estrogen levels challenge long-standing paradigms regarding the testosterone requirement for prostatic carcinogenesis. In addition, these findings raise questions about the role of estrogens in prostate cancer. [Table: see text] [Table: see text]
Satraplatin, an oral platinum analog, is active and synergistic with paclitaxel and docetaxel in prostate carcinoma models
Authors: Lamphere L. , Obermayr F. , Caligiuri M. , Unteregger G. , Rudoltz M. S. , Wosikowksi K. , Casazza A. M. 
Published: March 2020

14620 Background: Satraplatin is a novel oral platinum analog with potent cytotoxic and antitumor activity in preclinical models. Satraplatin showed activity in hormone refractory prostate cancer (HRPC) and other tumor types in Phase II trials. A pivotal Phase III trial evaluating satraplatin as 2nd-line therapy for HRPC completed accrual of > 900 patients in 2005. Satraplatin’s activity, safety profile and ease of administration make it attractive for combination regimens. Methods: Satraplatin and its active metabolite JM-118 were tested in vitro as single agents in the androgen-sensitive LNCaP and the androgen-insensitive PC-3 and DU-145 human prostate carcinoma (ca.) cell lines. For in vitro combination studies, PC-3 cells were treated with satraplatin or JM-118 either prior to, after, or concomitantly with paclitaxel or docetaxel. The PC-3 cell line was used for in vivo xenograft experiments in nude mice. Paclitaxel was given intravenously on Day 1, satraplatin orally on Days 2 to 6, and paclitaxel again on Day 8. Results: Satraplatin and JM-118 as single agents inhibited the growth of all three prostate ca. cell lines in vitro in a dose dependent fashion. IC50 values for JM-118 were < 1μM. Strong synergism was noted when PC-3 tumor cells were treated in vitro with paclitaxel or docetaxel followed by satraplatin or JM-118. Satraplatin administered orally inhibited the growth of PC-3 xenografts in nude mice. Treatment of advanced PC-3 tumors with paclitaxel (40 mg/kg) and satraplatin (35 mg/kg) was well tolerated and resulted in a Tumor Growth Delay equivalent to 3 Log Cell Kill, an effect superior to that of the single agents. Conclusions: In vitro, satraplatin and its metabolite JM-118 are active as single agents against human prostate ca. cells, and are synergistic with taxanes. In vivo, treatment with paclitaxel followed by satraplatin showed synergism without increased toxicity. These preclinical data support ongoing Phase I and II clinical trials that are evaluating combinations of satraplatin with paclitaxel or docetaxel. [Table: see text]
Increasing overall survival with neoadjuvant and concomitant hormonal therapy plus conformal radiotherapy for high risk prostate cancer patients
Authors: Cruz M. R. , Nakamura R. A. , Monti C. R. , Prestes J. C. , Trevisan F. A. , Ferrigno R. 
Published: March 2020

14641 Objective: To evaluate the value of neoadjuvant (NHT) and concomitant hormonal therapy (CHT) for high risk prostate cancer patients treated with conformal radiotherapy (3DCRT). Methods: From October 1997 to January 2002, 116 patients with high risk prostate cancer were submitted to 3DCRT and were analyzed retrospectively. High risk patients were defined as patients with PSA >20 ng/ml, and/or T3 clinical stage and/or Gleason score >7, or two factors of intermediate risk (PSA ≥10 and <20 ng/ml, T2b-T2c and Gleason score >7). The NHT and CHT were performed on 69 (59.5%) and 79 (68.1%) patients, respectively. The prostate and seminal vesicles median doses were 81 Gy (72–82.8) and 61.2 Gy (45–77.4) respectively. The median time from diagnosis to 3DCRT was 2,9 months (0.9–134.9). Results: On median follow-up of 54.5 months (13.5–93.9), the 5-year actuarial overall (OS) and 5-year biochemical progression-free survival (BPFS) were 84.3% and 64.7% respectively. The OS for patients submitted to NHT was 89.8% versus 76.4% for patients that were not submitted to (p = 0.0139). Patients that received CHT had an OS of 89.6% versus 73.4% for patients that did not receive CHT (p = 0.0201). Gleason score, clinical stage and seminal vesicles irradiation were significant to BPFS (p = 0.0372, p = 0.0412 and p = 0.0321 respectively). Conclusions: NHT and CHT increased OS of high risk prostate cancer of patients. Gleason score and clinical stage were important prognostic factors to BPFS. Seminal vesicles irradiation is recommended for high risk patients. No significant financial relationships to disclose.
Outcomes associated with retinoblastoma and c-myc gene expression in patients with testicular cancer: A ten-year experience
Authors: Astudillo-De La Vega H. , Ruiz-Garcia E. , Salcedo M. , Torres A. , De La Cruz J. A. , Benitez A. , Gariglio P. , Gutierrez-Delgado F. 
Published: March 2020

14656 Purpose: To determine and correlate the protein and mRNA expression of c-myc and Rb genes in normal testicular tissue and testicular cancer as possible markers of pharmacological response. Methods: Eleven fresh testicular cancer surgical specimens were obtained from untreated patients with histological diagnosis of seminoma (9/11) and non seminoma (2/11) during the period of 1992 to 1995. Age patient average was 35 (16–74). Two normal human testicular tissues also were evaluated as control. Single and double immunohistochemical assay was performed with peroxidase anti-peroxidase system using polyclonal antibody anti-pRb C-15 and monoclonal antibody anti- c-myc 1. Non radioactive in situ hybridization with cRNA probes was performed with cDNA from Rb (exons 2–27) and c-myc (exons 2,3). All seminomas were stage I and were treated with radiotherapy. Non-seminomas were stage III and were treated with chemotherapy. Results: Histological findings: Rb protein was expressed in mature cells toward the lumen of normal testicular tissue while c-myc was located in basal cells but decreasing the expression toward the lumen. High correlation between mRNA and protein levels for both genes was observed in normal testicular tissue. Rb protein and mRNA was absent in 6/11 (55%) tumors while the remaining showed a low level expression (45%). A high c-myc expression was observed in 6/11 (55%) seminomas specimens correlating in a few cases with absent Rb expression. Percentage of positive cells to c-myc gene expression (mRNA and protein) was highly increased in tumoral samples. Clinical findings: All patients with seminoma (9/11) and one of non seminoma (1/11) are alive and without tumoral activity a ten years of the diagnosis. A non-seminoma patient (1/11) have 11-year survival, a high expression of c-myc gene and absent retinoblastoma expression was observed in this case. Conclusion: The semiquantitative differences observed on c-myc and Rb gene expression in seminoma and non-seminoma tumors might correlate with the biological behavior including their high proliferation rate and the chemosensitivity. No significant financial relationships to disclose.
Survival of patients with testicular germ-cell tumors with poor prognosis secondary to liver metastases
Authors: Martinez-Cedillo J. , Aguilar J. L. , Morán-Mendoza A. , Arrieta O. , Cruz-Lòpez J. , Calderillo G. , Rivera-Lamas A. , Torreblanca-Montaño M. , Lara-Medina F. , De La Garza J. G. 
Published: March 2020

14657 Background: Most patients with disseminated germ-cell tumor have an excellent prognosis with cisplatin-based combination chemotherapy, although there have been described certain subgroups with a worse prognosis. The presence of liver metastases (LM) represents an independent cause of poor prognosis. This study reviews the clinical course and treatment results of patients treated at Instituto Nacional de Cancerología de México (INCan-Mex). Methods: The records of all patients with germ-cell cancer and LM between 1992 and 2002 were reviewed. Age, primary site, metastases site, number of metastasis sites, histopathology type, serum tumor markers (STM) levels, liver functional assay, number of LM and used chemotherapy were examinated. The overall survival (OS) and disease free survival (DFS) were analized with Kaplan-Meier method and Log Rank test. Results: Of 32 reviewed patients, median age was 24 (range 18–42 y). The primary site was testis in 27 patients and retroperitoneal in 5 patients. The number of metastasis sites was > 3 en all cases. All patients had nonseminomatous component, predominating choriocarcinoma (82%) and seminoma (78%). The 60% of patients had STM of poor prognosis. 50% of the patients had abnormal liver functional assay. 25 cases (78%) had multiple LM. First line chemotherapy had complete response (CR) in 2 patients, partial response with STM negative (PRM-) in 12 cases, partial response with STM positive (PRM+) 8, and progression in 9 patients. All patients were treated with cisplatin-based chemotherapy. No prognostic factors of chemotherapy response were determined. Only 11 cases underwent to resection surgery of retroperitoneal or pulmonary residual. No patients underwent to liver surgery. Five year OS of 32 cases were 50%, 34% with DFS, between the patients with superior response to chemotherapy (RC + PRM-) the OS and DFS was better in relation with minor response or progression (p < 0.05). The cases with RC in liver (11) were 5-year OS 100% and DFS 66% (p < 0.05). Conclusions: The clinical course and results of treatment in the 32 cases of the INCan-Mex were similar to the literature. This study represents the greatest individual serie reported. These patients with poor prognosis are candidates to innovative treatment modalities. No significant financial relationships to disclose.
A randomized multicenter phase II study on neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian carcinomas (PRIMOVAR)
Authors: Park-Simon T. , Jänicke F. , Ortmann O. , Hilfrich J. , Breitbach G. , Höss C. , Möbus V. , Thomssen C. , Diedrich K. , Kuhn W. 
Published: March 2020

15025 Background: In the past years the concept of neoadjuvant chemotherapy and interval laparotomy has emerged for patients with advanced ovarian cancer and unfavorable prognosis (e.g. diffuse peritoneal carcinosis). In a recent study on neoadjuvant chemotherapy higher tumor resection rates and longer median survival were demonstrated in patients with advanced ovarian carcinoma and ascites >500ml. Most studies use three cycles of preoperative chemotherapy. However, chemoresistant tumorclones may be induced by increasing number of preoperative chemotherapy cycles. The purpose of this study is to evaluate the optimal number of cycles prior to interval laparotomy. Methods: 67/73 patients with advanced serous ovarian carcinoma (FIGO IIIc n = 48, FIGO IV n = 19) and ascites >500ml were randomized into two arms, receiving either 2 (n = 33) or 3 (n = 34) cycles of Carboplatin (AUC5) and Docetaxel (75mg/m2) before interval laparotomy. Postoperatively, they received either 4 or 3 additional cycles. Response rate and postoperative residual tumor were evaluated. Results: Surgical response was assessed during interval laparotomy. At present 32 patients underwent tumordebulking. Partial remission was observed in 28/32 patients irrespective of the number of preoperative chemotherapy cycles. Two patients in each arm showed stable disease. Optimal cytoreduction was achieved in 25/32 patients. No severe adverse events were reported. Six of 73 patients were not eligible. Two patients were excluded due to therapy-unrelated events. In 4 patients ovarian cancer was excluded by laparoscopy prior to neoadjuvant chemotherapy. Conclusions: Neoadjuvant chemotherapy followed by interval laparotomy was safe and well tolerated. Diagnostic laparoscopy prior to neoadjuvant chemotherapy allowed differentiation of primary ovarian cancers from tumors of other origin. In these cases laparotomy could be circumvented. Optimal tumor reduction was achieved in a significant number of patients. Response rate and postoperative residual tumor were essentially the same in both arms. Our data indicate that two cycles of preoperative chemotherapy may be the preferential choice of therapy for future studies. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin and platinum in patients with advanced ovarian cancer in late relapse (>6 months)
Authors: Wei L. , Chen C. , Huang C. , Chien S. , Huang Y. , Cheng W. , Hsieh C. 
Published: March 2020

15035 Background: Platinum and doxorubicin have different mechanisms of action, show no cross-resistance, and their toxicities do not overlap. Because pegylated liposomaI doxorubicin (Lipo-Dox was manufactured by TTY Biopharm Company Ltd. in Taiwan) appears to be a promising form of delivering doxorubicin with decrease of some of the most problematic toxicities, a combination with platinum should be assessed. Methods: An open-label, non-comparative, single center phase II clinical trial. Eligible patients must have histologically proven advance ovarian cancer with two-dimensioned measurable disease or evaluable disease (defined as CA-125 ≥ 40 U/ml), who have been treated with one or two previous platinum- and taxane-based regimen. All patients will hospitalize for 24 hours for treatment. The dose of platinum is fixed (cisplatin at 75 mg/m2 or carboplatin at AUC=5) on D1 and the initial dose of pegylated liposomaI doxorubicin (Lipo-Dox) is 35 mg/m2 on D2 at a 4-week interval. Results: Twenty patients were enrolled from July 2002 to January 2004 and follow up until June 2004. All eligible patients are assessable for response and toxicity. The overall response rate was 80%. Of the 20 patients eligible for response evaluation, 10 (50%) patients had a complete response, 6 (30%) had partial response, 3 (15%) were with stable disease, and 1 (5%) showed progressive disease. An overall response (OR) was achieved in 80% of patients. In patients achieving an OR based on WHO criteria, median CA125 levels declined from 142 U/ml (range, 13–3670 U/ml) during the baseline to 26.5 U/ml (range, 5–375 U/ml) during the last cycle. Median time to response was 65 days (range, 12–188 days). Median duration of response was 471 days (range 146–1085 days). Furthermore, the median time to progression was 481 days (range, 138–1136 days). The main toxicity was myelosuppression, with grade 3 and 4 neutropenia in 3 patients, anemia in 4 patients, and leukopenia in 2 patients. Conclusions: Based on effectiveness and toxicity advantages, the combination of pegylated liposomaI doxorubicin (Lipo-Dox) and platinum should be considered in patients with advanced ovarian cancer in late relapse. No significant financial relationships to disclose.
Clinical experience of using docetaxel-cisplatin in the treatment of advanced ovarian cancer: A Bangladesh perspective
Authors: Mokhlesuddin M. , Akhter P. S. , Ahmed D. U. , Khan M. A. , Rahman M. A. , Islam T. 
Published: March 2020

15070 Background: Docetaxel is an active agent in the treatment of recurrent advanced ovarian cancer. We conducted a multi-center phase II study to evaluate the response rate, toxicity and survival of docetaxel-cisplatin regimen as first-line treatment of advanced ovarian cancer in Bangladeshi population. Methods: Forty chemotherapy-naïve patients of advanced epithelial ovarian cancer were recruited between October 1999 to March 2002. Eligibility criteria included stage Ic-IV patients, age 18–75 years, an ECOG performance status of 0–3 with adequate hepatic, renal and bone marrow function. Docetaxel 60 mg/m2 as 1 hour IV infusion and cisplatin 75 mg/m2 were given on day 1 every 3 weeks for a maximum of 6 cycles (average 5 cycles). Tumor responses and toxicities were evaluated by relevant investigations and survival was documented. Results: A total of 40 patients were enrolled. Median age was 44 years (age range 18–75 years). All the patients were evaluable for response. Overall response was observed in 32 patients (80%) with complete response rate 38% (12 patients), partial response rate 62% (20 patients). Stable disease was seen in 5 patients (12.5%) and progressive disease was in 3 patients (7.5%).Two years survival was documented in 62% patients. Toxicities were limited with grade 3 neutropenia in 10 patients (25%) and some non-hematological toxicities (including nausea, vomiting and fluid retention) in twenty-six patients (65%). No severe febrile neutropenia and no events of death were observed. Conclusions: The combination of docetaxel and cisplatin appears to be effective with manageable toxicities in patients with advanced epithelial ovarian cancer in Bangladeshi population. No significant financial relationships to disclose.
MGMT methylation status correlates with temozolomide-mediated radiosensitization in a panel of GBM orthotopic xenografts
Authors: Sarkaria J. N. , Carlson B. L. , Decker P. A. , Schroeder M. J. , Kitange G. J. , Ballman K. V. , James C. 
Published: March 2020

1509 Background: Lack of MGMT methylation in GBM tumors is associated with a worse outcome with combined radiation (RT) and temozolomide (TMZ) therapy, and it is unclear whether non-methylated tumors benefit from TMZ treatment. Methods: The potential benefits of concomitant or adjuvant TMZ relative to methylation status were evaluated in 10 GBM tumors established from patient samples and maintained by serial passage in mice. For each tumor line, 32 mice with established orthotopic xenografts were randomized to A) placebo, B) TMZ PO daily × 5 (120 mg/kg or 66 mg/kg, as indicated) C) RT, 2 Gy bid × 10 fx., D) combined TMZ and RT, and mice were followed until moribund. Efficacy was evaluated by regression modeling and Kaplan-Meier statistical analyses. Results: Six lines with non-methylated MGMT (GBM10, 14, 26, 28, 36, 43) and 4 with methylated MGMT (GBM8, 12, 16, 34) were evaluated, and complete results are available in 6 lines. In all tumor lines and at both dose levels, there was a significant benefit for TMZ relative to placebo (p<0.003). Both methylated tumors (GBM8 and 12) and one non-methylated tumor (GBM14) were markedly sensitive to TMZ with greater than a 50 day extension in survival with monotherapy. Individually and in a pooled analysis, there was no evidence for a synergistic interaction between TMZ and RT in the non-methylated tumors (p=0.91 for pooled analysis). In contrast, there was a striking degree of synergy in GBM12 (p<0.001) and at least additive effects of combined treatment in GBM8 (5 of 8 mice still surviving in the RT/TMZ arm). In a pooled analysis of these 2 MGMT methylated tumors, there was a trend towards synergy (p=0.11). Conclusions: TMZ treatment did not sensitize MGMT non-methylated tumors to radiation, and with one exception, these non-methylated tumors were only modestly sensitive to TMZ alone. In contrast, treatment with TMZ appears to sensitize MGMT-methylated tumors to radiation and monotherapy is associated with marked and significant benefit. [Table: see text] No significant financial relationships to disclose.
Results of a phase II trial of h-R3 monoclonal antibody (nimotuzumab) in the treatment of resistant or relapsed high-grade gliomas in children and adolescents
Authors: Bode U. , Buchen S. , Janssen G. , Reinhard T. , Warmuth-Metz M. , Bach F. , Fleischhack G. 
Published: March 2020

1522 Background: Children and adolescents suffering from high grade gliomas (HGG) have a poor prognosis when they relapse during or after primary treatment. Thus novel therapeutic approaches as the inhibition of growth-signalling pathways are needed. This multicentre phase II trial was designed to explore the feasibility and efficacy of the h-R3 monoclonal anti-EGFR antibody (Nimotuzumab) in the treatment of these patients. Methods: Pediatric patients with glioblastoma multiforme, anaplastic astrocytoma or intrinsic pontine glioma (PG) with radiologically proven progressive disease following primary or relapse treatment were eligible to the study. The treatment consisted of an induction therapy including a weekly short infusion of 150 mg/m2 Nimotuzumab for six weeks, and in case of non-PD a subsequent consolidation therapy of four infusions in a three week interval. The response was documented by MRI in week 8 and 21. Results: Between June 2004 and August 2005 34 patients aged 5.0 to 17.4 years (median 10.9 years) were enrolled in this study. According to RECIST 12 out of 34 patients showed response (PR n=1, SD n=11) in the MRI of week 8 after the induction therapy with a median change in the largest diameter of the index lesion of −5% (−39 to +16%) accompanied by clinical deterioration in four and markedly clinical improvement in two patients. Surprisingly, 9 PR/SD were seen in the 14 patients with PG. Eight patients continued with the consolidation therapy. So far 5 out of 8 Patients are evaluable for response after consolidation therapy and showed three PR, one SD and one PD in week 21. Eight patients with consolidation therapy are free of progression for a median of 7.5 months (1.2–13.2 months). No severe side effects related to the study medication were observed. Conclusions: These data suggest that the repeated application of Nimotuzumab is well tolerated and safe. It has cytotoxic efficacy in heavily pre-treated relapsed HGG, especially in intrinsic pontine glioma. A phase III study for patients with newly diagnosed PG is warranted. [Table: see text]