bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of gynecological malignancies based on pathologic reports in five general hospitals in Tehran (1995–2005)
Authors: Momtahen S. , Sadreddin Kazzazi A. , Kadivar M. 
Published: March 2020

5550 Background: Various histological types of gynecological tumors may develop from different etiological aspects. The observed differences in cancer incidence are mainly due to different individual and social risk factors. Step toward establishing a nation wide registry is being taken in this study. Methods: To give a relative frequency of female genital tract malignant tumors in Iran we designed a cross-sectional study included 450 women with definite diagnosis of gynecological cancer based on pathologic reports in five pathologic centers, Iran University of Medical sciences, Tehran, 1995–2005. WHO classification of gynecological tumors and International Federation of Gynecology and Obstetrics (FIGO) were used as basis of study. Spss 14 and correlation test was used for data analysis. Results: The average age of diagnosis was (50±0.7). 49.6% were menopausal. 82.7% were multipar. 89.8% were nonsmoker. 9.3% had history of using OCP. Ovarian cancers (55.5%), uterus cancers (24.9%) and cervical cancers (19.6%) were diagnosed. Surface epithelial-stromal tumor was the most frequent type of ovarian tumors (78.4%). Endometrial adenocarcinoma (70.5%) and squamous cell carcinoma (83%) were most frequent types of uterus and cervical cancers respectively.Well differentiated tumors were seen in 45%, 37% and 36% of uterus, cervical and ovarian tumors. In tumors of uterus and cervix the most frequent stage of diagnosis was stage IIA. The most metastatic diagnosed cases were seen between ovarian tumors (39.7%). Conclusions: Comparison with data published as review articles in NEJM till 2006, the most frequent gynecologic cancer in our study (ovarian cancer) is different to them; also the median age of our patients is lower than them. [Table: see text] No significant financial relationships to disclose.
A phase I trial of the proteosome inhibitor PS-341 in combination with carboplatin in platinum and taxane resistant ovarian cancer patinets
Authors: Landen C. N. , Coleman R. , Milam M. R. , Johnston T. , Iyer R. , Gershenson D. M. , Ramirez P. 
Published: March 2020

5558 Background. PS-341 (Millenium Pharmaceuticals, Inc.), a proteosome inhibitor, affects p53, NFκB, cell adhesion molecules, and sensitivity to cytotoxic agents to promote apoptosis and inhibit metastasis in cancer cells. PS-341 alone rarely causes myelosupression or renal toxicity, and therefore is an attractive agent to use in combination with cytotoxic chemotherapy. This phase I study evaluates the safety, dose-limiting toxicities (DLTs), and optimal dose of PS-341 when combined with carboplatin in ovarian cancer patients with recurrent, platinum- and taxane-resistant disease. Methods: After IRB approval, patients with recurrent ovarian cancer, platinum and taxane resistant (progression on platinum and/or taxane therapy or recurrence within 6 months of completing platinum and/or taxane therapy), measurable disease, and performance status 0–2 were eligible and enrolled after giving informed consent. As guided by toxicity and pharmacokinetic data from single-agent phase I trials, PS-341 was administered on days 1, 4, 8, and 11 by IV push every 28 days with carboplatin (AUC 5) on day 1. Four dose levels were evaluated: 0.8, 1.0, 1.3, and 1.5 mg/m2. Dose was escalated if 0 of 3 or 1 of 6 patients had a DLT. The MTD was defined as 2 or more patients out of 6 with a DLT. Results: 21 women (median age 63, range 43–83), were treated with carboplatin and PS-341 at 0.8mg/ m2 (n=6), 1.0 mg/m2 (n=3), 1.3 mg/m2 (n=6), or 1.5 mg/m2. (n=6). At each level, respectively, there were 1, 0, 1, and 3 DLT’s attributable to PS- 341; all were grade 3, consisting of fatigue (n=3), nausea/vomiting/dehydration (n=1), and anorexia/dehydration/syncope (n=1). There were no Grade 4 toxicities. Common grade 2 toxicities included fatigue (n=12), nausea (n=10), anorexia, anemia, and dyspnea (n=7 each). 18 patients evaluable for response had stable disease (SD) or progression of disease (PD): at 0.8 mg/m2, SD=2, PD=3; at 1.0 mg/m2, PD=3; at 1.3 mg/m2, SD=3, PD=3; at 1.5 mg/m2, SD=3, PD=1. Median duration of stable disease was 4 months (range 3–10). Conclusions: The recommended dose of PS-341 in combination is 1.3 mg/m2. Treatment was well-tolerated with reversible side effects and no grade 4 toxicities, and at the optimal dose, there was a 50% rate of stable disease. No significant financial relationships to disclose.
HER2 overexpression and amplification in advanced ovarian cancer (AOC): Treatment with trastuzumab—A GINECO study
Authors: Guastalla J. P. , Allouache D. , Combe M. , Weber B. , Cretin J. , Curé H. , Mousseau M. , Paraiso D. , Camilleri-Broët S. , Pujade-Lauraine E. 
Published: March 2020

5559 Background: Variable rates of HER2 protein overexpression and gene amplification have been reported in AOC. Trastuzumab (Herceptin [H]) has been tested only as single agent and has shown a 7% response rate (RR) in heavily pre-treated AOC patients (pts) with 3+ and 2+ HER2 immunostaining (IHC) (Bookman MA et al, J Clin Oncol 2003). GINECO has explored the combination of H with paclitaxel (T) and carboplatin (C) in pts with resistant AOC (< 6 months) and HER2 gene amplification. Methods: 321 AOC pts were centrally screened for HER2 status (243 pts in first-line and 78 relapsing pts). All positive (3+) and doubtful (2+) cases were screened by fluorescence in-situ hybridisation (FISH). Pts with HER2 gene amplification, normal left ventricular ejection fraction (LVEF) and resistant relapse after first or second line of chemotherapy including TC were treated with T (175mg/m2, 3h), C (AUC 5) and H (9mg/kg first course, 6mg/kg subsequent courses) every 3 weeks. Results: Of the 321 cases tested, 22 (6,7%) were HER2+ by IHC and FISH. Only 7 pts (32%) with a median age of 56 (range: 48–70) met the eligibility criteria of the trial. Pts had measurable lesions (n=4) or elevated CA 125 level + non-measurable lesions (n=3). Three pts had complete response (6, 7+ and 24+ months) and 2 had stable disease (3 months). Toxicity was moderate: febrile neutropenia, Gr3 infection, Gr2 neurotoxicity and decrease of LVEF after 23 cycles of H were observed in one patient respectively. Conclusions: HER2 overexpression/amplification is low in advanced ovarian carcinoma (6,7 %). In this small prospective cohort of resistant patients, 3 of 7 have achieved complete remission when adding Trastuzumab to conventional chemotherapy. No significant financial relationships to disclose.
A contemporary analysis of the ability of preoperative serum CA-125 to predict primary cytoreductive outcome in patients with advanced ovarian, tubal, and peritoneal carcinoma
Authors: Zivanovic O. , Chi D. S. , Eisenhauer E. L. , Sonoda Y. , Levine D. A. , Brown C. L. , Barakat R. R. 
Published: March 2020

5572 Background: We previously reported that preoperative CA-125 may predict primary cytoreductive outcome in patients (pts) with stage III ovarian carcinoma. We performed a contemporary analysis of the ability of preop CA-125 to predict cytoreductive outcome in advanced ovarian, tubal and peritoneal carcinoma. Methods: In 1/01, we initiated a programmatic change in our primary surgical approach to advanced gynecologic malignancies using extensive upper abdominal procedures to achieve maximal cytoreduction. We reviewed the records of all pts with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at our institution between 1/01 and 4/05. Results: The study cohort included 277 pts. Primary disease site was: ovary; 232 (84%); tubal, 9 (3%); and peritoneum, 36 (13%). Stage was: IIIA, 6 (2%); IIIB, 12 (4%); IIIC, 215 (78%); and IV, 44 (16%). Tumor grade was: I, 6 (2%); II, 30 (11%), III, 235 (85%), and unknown, 6 (2%). Cytoreductive outcome was: no gross residual disease (RD), 68 (25%); ≤ 1 cm RD, 153 (55%); and > 1 cm RD, 56 (20%). There was no threshold CA-125 level that accurately predicted cytoreductive outcome. With CA-125 values > 500 U/mL, 50% (57/113) of pts required extensive upper abdominal surgery to achieve RD ≤ 1 cm, compared to 27% (25/93) for those with CA-125 < 500 U/mL (P = 0.03). The table demonstrates the number of pts cytoreduced to = 1 cm RD in relation to preoperative serum CA-125 and the proportion of pts who needed extensive upper abdominal surgery to achieve this degree of cytoreduction. Conclusions: After the incorporation of extensive upper abdominal procedures, preop CA-125 did not predict the primary cytoreductive outcome of pts with advanced ovarian, tubal or peritoneal carcinoma. With preoperative CA-125 > 500 U/mL, extensive upper abdominal procedures were necessary in 50% of pts to achieve residual disease ≤ 1 cm. These data may be useful as part of preoperative surgical counseling and planning. [Table: see text] No significant financial relationships to disclose.
Phase II study for the suboptimally debulked advanced ovarian cancer: Intravenous platinum followed by interval debulking surgery and intravenous paclitaxel + intraperitoneal cisplatin (KCOG9812 study)
Authors: Tsubamoto H. , Ito K. , Itani Y. , Ito K. , Iijima T. , Hosokawa K. , Adachi S. 
Published: March 2020

5576 Background: Intraperitoneral administration (IP) of cisplatin is recommended by National Cancer Institute for the patients with optimally debulked epitherial ovarian cancer (EOC). However, the advantage is not determined for the suboptimally debulked EOC after the initial surgery. We conducted a phase II study of cisplatin IP after the interval debulking surgery (IDS) following 3 cycles of intravenous platinum. Methods: The initial planned sample size was 30. Eligible patients had previously untreated, histologically confirmed EOC or primary peritoneal carcinoma (PPC) of FIGO stage IIIB-IV with suboptimal (> 1 cm) residual disease. Carboplatin AUC 4 iv d1 and cisplatin 50 mg/sqm iv d3 q21d for 3 cycles. After IDS, paclitaxel 175 mg/sqm iv d1 (or paclitaxel 60 mg/sqm iv d1,d8,d15) and cisplatin 75mg/m2 IP q21d for 4 cycles. Primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and toxicity. Results: 33 patients were enrolled since 1998 till 2005. The median age was 55 (range 19–77). ECOG PS 0/1/2 = 33%/36%/31%; stage IIIB/IIIC/IV = 6%/64%/30%; 91% serous papillary histology. Optimal interval debulking surgery was possible in 85%: none (61%), < 1 cm (24%). Grade 3 or 4 (CTCAE ver.3) non-hematologic toxicity was seen in one patient of neurotoxicity. Grade 3 or 4 hematologic toxicities include: neutropenia (37%), infection (4%), thrombocytopenia (11%). 55% were completed the treatment schedule. The reasons for discontinuing were drug resistance (12%), subileus (4%), elevation of serum creatinine (12%), G3 neurotoxicity (4%), IP catheter block (12%) and infection (4%). Primary recurrent sites of total 20 patients before the second line chemotherapy or surgery were peritoneal cavity (30%), distant metastasis (45%), retroperitoneal lymph nodes (15%), and elevation of serum CA125 (10%). Median PFS was 24 months; median overall survival was 48 months; median follow-up was 36 months (range 15–100). Conclusions: This treatment including cisplatin IP after IDS for the patients with the initially suboptimally debulked EOC was feasible, and showed good prognosis with the small number of the intraperitoneal recurrence. [Table: see text]
Evaluation of the prognostic significance of human kallikrein 8 protein expression levels in advanced ovarian cancer by using automated quantitative protein analysis
Authors: Kountourakis P. , Psyrri A. , Scorilas A. , Markakis S. , Kowalski D. , Camp R. L. , Diamandis E. P. , Dimopoulos M. A. 
Published: March 2020

5581 Background: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 8 (hkl8) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Materials and Methods: A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of kallikrein 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Results: Mean follow-up time of the cohort was 34.35 months. One hundred twenty six of 150 cases had sufficient tissue for AQUA analysis. There was association between tumor mask hk8 protein expression levels and clinicopathological variables including grade (p=0.0011), residual disease (p=0.0063),clinical response to chemotherapy (p=0.0346). In univariate survival analysis there was a correlation between hk8 tumor mask expression and 5 years progression-free survival. Low hk8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterized prognostic variables, tumor hkl8 expression level retained its prognostic significance for disease free survival (95%CI: 0.341–1.027, p=0.0468). Conclusions: Human Kallikrein 8 is an adverse prognostic factor in patients with ovarian cancer.The possibilities that hK8 may be suitable candidate as diagnostic, prognostic marker and therapeutic target merit further investigation. No significant financial relationships to disclose.
Novel phase II study design of MORAb-003, a monoclonal antibody against folate receptor alpha in platinum-sensitive ovarian cancer in first relapse
Authors: Phillips M. , Armstrong D. , Coleman R. , Weil S. , Arseneau J. , Glenn D. , Puls L. , Senzer N. , Torres J. , White A. 
Published: March 2020

5583 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 (M3) is a humanized monoclonal antibody to FRA. Binding of M3 to FRA blocks phosphorylation by Lyn kinase; mediates FRA-positive tumor cell killing; and suppresses tumor growth in xenograft models. High-dose M3 is non-toxic in monkeys. A phase 1 study showed no significant AEs and suggestions of efficacy in platinum-resistant EOC. This phase 2 efficacy study will determine the efficacy of M3 in platinum-sensitive EOC in first relapse, either as a single agent (SA) in asymptomatic relapse, or in combination with platinum and taxane (P/T) in symptomatic relapse, and to maintain a second response. Methods: Subjects with EOC in first relapse are eligible. For CA125 elevation without symptoms (± measurable disease) the subject receives SA M3 until progression. For symptomatic relapse the subject receives P/T and M3. Subjects with CR or PR receive SA M3 maintenance therapy with the objective of prolonging the second remission longer than the first. Endpoints include CA125 and CT scans. ORR and PFS will be determined for each arm. Results: To date, 15 subjects have been treated, 8 in combination therapy and 7 on single-agent M3. No significant drug-related adverse events have been reported. All subjects treated with the combination of M3 and P/T for symptomatic relapse who have reached at least the first evaluation point have achieved a normalization of CA125 and reduction of tumor size (CR or PR) by CT scan using RECIST criteria, including 3 of 3 subjects with first remissions of 6 to 9 months. Early responses have been observed in the SA M3 treatment arm. Conclusions: This first phase 2 study will determine the efficacy of M3, either as SA or in combination with P/T chemotherapy to achieve a meaningful response rate in EOC in first relapse, and to maintain the second remission longer than the subject’s own first remission. These data will be used to define the most effective phase of disease in which to use M3, and to focus a pivotal study on the area of greatest efficacy. The early results continue to demonstrate activity of M3 in EOC. No significant financial relationships to disclose.
Comparative phase II study of intraperitoneal (IP) versus intravenous (IV) carboplatin administration with IV paclitaxel in patients with bulky residual disease after primary debulking surgery for epithelial ovarian or primary peritoneal cancer: A Sankai Gynecology Study Group (SGSG) study
Authors: Fujiwara K. , Nagao S. , Kigawa J. , Noma J. , Akamatsu N. , Miyagi Y. , Numa F. , Okada M. , Aotani E. , Terakawa N. 
Published: March 2020

5584 Background: To assess the anti-tumor effect and safety of IP carboplatin (C) administration comparing with IV C administration in combination with IV infusion of paclitaxel (P). Methods: This is a non-randomized comparative phase II trial. Eligible patients were those with histologically confirmed epithelial ovarian or primary peritoneal cancer who received initial surgery and ended up with residual disease >= 2 cm. They must have reasonable hematological, hepatic, renal function before receiving chemotherapy. The patients received either of the following treatment arms; IP Arm: IV P 175 mg/m2 over 3h followed by IP C AUC6, IV Arm: IV P 175 mg/m2 over 3h followed by IV C AUC6. The treatments were scheduled to repeat 6–8 cycles. Interval debulking surgery was allowed after 3 to 5 cycle of treatment. Each participating institution had to declare, before the study was opened, which of the treatment arms the patients from the institution would be entered. Primary endpoint was a response. Secondary endpoints were toxicity and progression-free survival (PFS) and overall survival (OS). Target accrual was 30 patients in each arm. Results: Total accrual was 26 patients for IP arm and 30 patients for IV arm between 2001 and 2005. The study was closed early, because of the conflict of protocols for IP treatment. Eligible patients were 24 in IP Arm and 25 for IV arm. Median number of treatment cycle was 6 for both arms. Although the difference was not statistically significant, response rate was better in the IP Arm. Response rates were 83.3% (95%CI: 62.6%-95.3%) for IP Arm and 60.0% (95%CI: 38.7%-78.9%) for IV Arm. As of median followup of 31 months, median PFS is 25 months for IP Arm and 21 months for IV Arm,. Median OS is not reached for IP Arm, and 52 months for IV arm. Incidences of hematological and non-hematological toxicities were essentially the same on both arms. Conclusions: IP administration of C may be a better treatment strategy for epithelial ovarian and primary peritoneal cancer patients. A randomized phase III trial including bulky residual disease for comparison of IP and IV carboplatin treatment. No significant financial relationships to disclose.
Increased risk of cervical cancer in high-risk families with and without mutations in the BRCA1 and BRCA2 genes
Authors: Rhiem K. , Fischer C. , Bosse K. , Wappenschmidt B. , Schmutzler R. K. 
Published: March 2020

5588 Background: In BRCA germline mutation carriers increased risks for cancer at other sites than breast and ovary have been reported. Methods: To evaluate the risk of BRCA-associated cancers, we conducted a cross-section analysis in 4405 individuals from 409 families with BRCA1 (n=86) or BRCA2 mutations (n=53) and 270 high risk BRCA1/2 negative families ascertained by the Familial Breast and Ovarian Cancer Center Cologne. We considered proven mutation carriers, individuals affected by breast and ovarian cancer and their first degree relatives and identified 921 individuals from BRCA1 (604 female; 317 male), 571 from BRCA2 (365 female; 206 male) and 2913 from BRCA1/2 negative (1938 female; 975 male) families that suffered from 677 cancers other than breast and ovarian cancers. Relative risks (RR) of the study group compared to the general population were evaluated by the standardized incidence ratio (SIR), using data from two German Cancer Registries. Results: The risk for cervical cancer is significantly increased in women from BRCA1 and BRCA2 positive (RR=4.59, 95% CI=2.20 to 8.44, and RR=3.69, 95% CI=1.20 to 8.61; p=<0.001) and from BRCA1/2 negative families (RR=2.97, 95% CI=1.88 to 4.45). Moreover, the risk for pancreatic cancer in women from BRCA2 positive and BRCA1/2 negative families as well as the risk for prostate cancer in men from BRCA2 positive families is increased (RR=5.10, 95% CI=1.65 to 11.90; RR=1.98, 95% CI=1.02 to 3.46; RR=2.09; 95% CI=1.00 to 3.84). Conclusions: We here report an increased risk of cervical cancer for women from BRCA1 and BRCA2 positive and from BRCA1/2 negative high risk families, respectively. These results are in line with other studies in BRCA1 and 2 positive individuals and should be considered in the clinical risk management of these individuals. No significant financial relationships to disclose.
Role of -2518 MCP-1 polymorphism in cervical cancer development
Authors: Coelho A. P. , Nogal A. , Pereira D. , Matos A. , Sousa B. , Araújo A. , Catarino R. , Medeiros R. 
Published: March 2020

5594 Background: Cervical cancer (ICC) and squamous intraepitelial lesions of the cervix uteri (SIL) constitute serious health problems to women worldwide. ICC occupies the second place in the list of tumours afflicting women. Around 470,000 new cases are diagnosed annually, 80% of which in less developed countries and near half of them resulting in death of the women. MCP-1 chemokine is the main determinant of tumour associated macrophages (TAM) content in the squamous cell carcinoma of the uterine cervix. The aim of our study was the evaluation of the association between the -2518 MCP-1 polymorphism (a biallelic G/A functional polymorphism) and susceptibility to cervical intraepithelial lesions and cervical cancer development. Methods: We analyzed 898 samples of DNA, of which 420 corresponded to healthy women (control group), 130 to women with low and high-grade cervical intraepithelial lesions and 348 to women with cervical cancer. The analysis of the polymorphism and the evaluation of the corresponding genotypes were performed with the PCR-RFLP methodology. Analysis of data was performed using the computer software SPSS for windows. Results: The analysis of the genotipic frequencies of the -2518 MCP-1 genotypes indicates that women carrying genotypes with the G allele present a 29.2% protection for the development of intraepithelial lesions of the cervix uteri (OR=0.708; 95% CI: 0.503–0.998; P=0.048) and a 33.5% protection for the development of squamous cell carcinoma of the cervix uteri. It was also possible to observe an association between the waiting time to onset of cervical cancer and the polymorphism: 59 years for women carrying genotypes with the G allele (95% CI: 56–61years) and 53 years for women with the AA genotype (95% CI: 52–57 years; P=0.005). Also, women with genotypes carrying the G allele present a 2.5 fold higher risk for the progression from early stages of invasive cervical carcinoma (I/II) to clinically more advanced stages (III/IV) (OR=2.26; 95% CI: 1.09–4.67; P=0.026). Conclusions: These findings suggest a role of the -2518 MCP-1 polymorphism in the molecular mechanisms that lead to cervical cancer development and progression. No significant financial relationships to disclose.