bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum YKL-40 levels in patients with cervical cancer are elevated compared to patients with cervical intraepithelial neoplasia and healthy controls
Authors: Johansen J. S. , Roslind A. , Palle C. , Christensen I. J. , Nielsen H. J. , Price P. A. , Nielsen D. , Mosgaard B. 
Published: March 2020

5047 Background: YKL-40 is secreted by cancer cells, macrophages and neutrophils. The exact function of YKL-40 is unknown. It may be a growth or differentiation factor, play a role in angiogenesis or protect against apoptosis. High serum YKL-40 is associated with poor prognosis in breast-, colorectal-, ovarian-, prostate-, small cell lung cancer and malignant melanoma. The aim was to examine serum YKL-40 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in pretreatment serum samples from 116 patients with cervical cancer (FIGO stage Ia (N = 5), Ib (N = 55), II (N = 27), III (N = 25) and IV (N = 4); median age 50, range 27–87 years) and 152 patients with cervical CIN (34 years, 20–80 years). The controls included 63 healthy women undergoing sterilization (36 years, 25–59 years) and a group of 134 healthy women (51 years, 18–79 years). Results: Serum YKL-40 was increased (p < 0.001) in the patients with cervical cancer (median 76 μg/l, range 20–2310) compared to patients with CIN (45 μg/l, 20–288), women undergoing sterilization (37 μg/l, 20–125) and healthy women (43 μg/l, 20–172). Patients with CIN had slightly elevated serum YKL-40 levels. Serum YKL-40 increased with increasing stage (Ia: median 36 μg/l, range 26–137; Ib: 56 μg/l, 20–984; II: 92 μg/l, 28–2310; III: 163 μg/l, 40–1474; and IV: 224 μg/l, 137–391; p < 0.001 Kruskal-Wallis test). All stage IV patients, 72% stage III, 52% stage II, 24% stage Ib, 40% stage Ia and 13% of patients with CIN had elevated serum YKL-40 compared to healthy controls (95th percentile). Patients with squamous cell carcinoma had higher serum YKL-40 (median 92 μg/l, range 27–2310, N = 86) compared to patients with adenosquamous (67 μg/l, 20–93, N = 9, p = 0.027) and adenocarcinoma (43 μg/l, 20–1472, N = 20, p < 0.001). Conclusion: Median serum YKL-40 is elevated in patients with stage Ib - IV cervical cancer. The serum level of YKL-40 seems to be correlated to the stage. No significant financial relationships to disclose.
Lymphatic mapping and parametrial lymph nodes identification in patients with early stage cervical cancer
Authors: Li B. , Wu L. , Li X. , Zhang X. , Zhang W. , Gao J. 
Published: March 2020

5050 Background: The purpose of this study was to determine the presence, distribution, and metastasis incidence of parametrial lymph nodes (PLN) of patients with cervical cancer, and to investigate the role of lymphatic mapping and topographic section in PLN identification. Methods: Sixty patients with early stage (Ib∼IIa) cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were included in the study. Before surgery 4 ml methylene was injected into the cervix around the tumor. The blue-dyed lymph nodes were identified as sentinel lymph nodes (SLN) during operation. An immediate topographic section on uterine specimen was performed to separate the PLNs from parametria for pathologic examination. Results: Ninety five PLNs were presented in 38 (63.3%) of 60 specimens, with a mean size in diameter as (0.67±0.24)cm, and 57 (60.0%) of PLNs were located parallel to the uterine artery through the entire broad ligament. After lymphatic mapping, 69 (72.6%) of PLNs was dyed and found out as SLNs. Parametrial metastasis was found in 12 (20.0%) patients, and parametrium was the only site containing positive nodes in 2 patients with parametrial metastasis. On routine pathologic evaluation, 17 PLNs were found to be positive. Among the remaining 78 PLNs, multilevel sectioning in conjunction with immunohistochemical analysis was carried out and identified 3 other PLNs containing micrometastases. Conclusions: The study showed that PLNs were often found in the parametria, and these nodes often contained metastatic diseases, which were often overlooked. Lymphatic mapping followed by meticulous topographic section is feasible in PLN identification in patients with cervical cancer. No significant financial relationships to disclose.
HistoScanning, a new device to enhance ultrasound’s contribution to clinical assessment of pelvic masses
Authors: Bleiberg H. , Akakpo J. , Granberg S. , Sideri M. , Mashiach R. , Autier P. , Nir D. 
Published: March 2020

5056 Background: HistoScanning (HS) is a medical device developed to improve interpretation of echography. Ovarian (OV) HistoScanning (OVHS) performs computerized analysis of voxel files generated during transvaginal ultrasonography (TVS). OVHS was integrated into a protocol for investigation of ovarian pathologies, primarily cancer (OVCa). Methods: A study was initiated; a/ to standardize the echography procedure, b/ to evaluate OVHS ability to differentiate cancerous to non-cancerous pelvic masses under appropriate conditions. Women (W) ≥18 years old planned to have complete removal of ≥1 OV were eligible. Exclusion criteria include previous diagnosis of OV cancer, pelvic surgery, radiotherapy or chemotherapy for breast or OVCa. Real 3D-TVS were performed before surgery and the voxel data sent to AMD. After OVHS results were locked in the study’s data base, pathological reports were sent to the clinical research organization and the OVHS results were compared to histology. Results: From 09.2004 to 07.2005, 486 data files were obtained from 9 institutions. 120 were used for calibration, 97 had no surgery, and 269 met the protocol requirements. Pelvic histology includes normal OV (87), benign tumors (T) (78), past endometriosis (9), borderline cancers (21), adenocarcinomas (53), carcinomatosis (12), metastases (4) and other cancers (3), others (2). 91 cancers were correctly diagnosed (sensitivity 98%). Reason for false negatives was: lack of voxel data for the lesion (1) and pathology volume bellow US resolution (‘Cystadenofibroma with foci of low malignant potential; Borderline‘) (1). When gain used during TVS was appropriate, the false positive (FP) rate was 3% for normal tissues and 17% for benign tumors. When gain used was inappropriate, FP rate was 10% and 41%, respectively. Conclusion: OVHS seems highly sensitive for the diagnosis of pelvic masses while having an acceptable specificity. A study using 3D-TVS performed with controlled gain level is ongoing. [Table: see text]
Stratification of the normal range of CA125 after chemotherapy as a predictive factor in carcinoma of the ovary
Authors: Nadal R. M. , Ojeda B. M. , Artigas V. , Bogunà I. , Gich I. , Ribé A. , Prat J. , López López J. , Barnadas A. 
Published: March 2020

5059 Background: CA125 is an accurate and reliable marker for monitoring the response to treatment and detecting early relapse in ovarian cancer. The implications of the variation of its normal range are not known.The purpose of this study was to evaluate such variations as a prognostic indicator after first-line chemotherapy Methods: Over a 7 years period (1998–2005), 114 patients (pts) were treated with standard chemotherapy regimen for FIGO stage Ic-IV epithelial ovarian cancer. The median age was 63 years old (24–87) years. The tumors were classified: 56% serous, 12% endometroid, 16% poorly differentiated and 16% clear cell carcinomas. FIGO stage: 12 (11%) Ic, 14 (12%) II, 72 (63%) III, 16, (14%) IV. After surgery, 90% of the patients received a median of 6 cycles/patient with platinum based (cisplatin or carboplatin) chemotherapy in combination with taxane. Serial measurement of CA12.5 had been made before each cycle of chemotherapy and response was assessed according to RECIST or Rustin criteria. Median follow-up has been 31 months. 87 pts achieved levels below 35 u/ml after completion of treatment. The nadir value of CA125 was stratified into three arbitrary groups: group 1, ≤ 10 U/ml, group 2, 11–20 U/ml, and group 3, 21–35 U/ml. The χ2/Fisher’s exact test was used to examine patients characteristics for categorical variables. Survival analysis was performed by Kaplan-Meier method with long-rank test for determining statistical significance. Results: No statistical relationship between FIGO stage and gross residual tumor vs nadir groups (p = 0.48 and p = 0.2) was found. Median duration of progression free survival according to 3 groups was 34, 20, 14 months, respectively (p= 0.003). The median overall survival for the group 1 is not yet available, however, the corresponding median overall survival for groups 2 and 3 were 3.8 and 2.7 years, respectively (p = 0.006) Conclusions: Within normal range, the differences between CA125 levels could add prognostic information and stratify patients according to the risk of progression. No significant financial relationships to disclose.
CA125 nadir as a prognostic factor in advanced ovarian carcinoma: A retrospective study of 84 patients achieving clinical CR
Authors: Tanabe H. , Katsumata N. , Matsumoto K. , Nishio S. , Kato Y. , Yonemori K. , Kouno T. , Shimizu C. , Ando M. , Fujiwara Y. 
Published: March 2020

5060 Background: There have been few reports of the relationship between CA125 nadir and the prognosis in patients with advanced ovarian carcinoma (AOC) who achieve a complete clinical response by multivariate analysis. Methods: CA125 nadir and the prognosis after the initial therapy (debulking surgery + first line chemotherapy) were retrospectively investigated in patients (pts) who had AOC meeting the criteria below and received therapy at National Cancer Center Hospital, between 1998 and 2004. The eligibility criteria were: 1) histological diagnosis of mullerian carcinoma, 2) FIGO stages III and IV, 3) a combination of platinum and taxane was administered as the first line chemotherapy, and 4) achieved clinically defined complete response (CR) after the initial therapy (ie, no cancer-related symptoms; normal physical examination, computed tomography scan of the abdomen/pelvis and chest x-ray). The possibility of CA125 nadir being a prognostic factor was investigated in pts who met these criteria by multivariate analysis (age (<50 years or 50 years≤), stage (III or IV), histological type (serous adenocarcinoma (serous) or non-serous), residual tumor diameter (<2 cm or 2 cm≤) and CA125 nadir (<10 U/ml or 10 U/ml≤)) using the Cox regression model. Results: There were 84 pts with a median age of 55.5 years (26–74). The stage was III in 59 pts and IV in 25 pts, the histological type was serous in 71 pts and non-serous in 13pts, and the residual tumor diameter was <2 cm in 72 pts and >2 cm in 12 pts and the median of CA125 before the initial therapy was 535 U/ml (13–28190), the CA125 nadir was <10 U/ml in 54 pts and 10 U/ml≤ in 30 pts, respectively. Regarding the prognosis, the median progression free survival (PFS) was 19 months (6–82), and the median overall survival (OS) was 36.5 months (10–82). By multivariate analysis, the CA125 nadir was significantly associated with the prognosis (hazard ratio of PFS was 0.39 (95% CI, 0.21–0.71), hazard ratio of OS was 0.28 (95% CI, 0.11–0.72)). Conclusion: CA125 nadir is a prognostic factor in patients with AOC who achieved clinically defined CR after the initial therapy, when the cut-off value was set to 10 U/ml. CA125 nadir may be an important factor for identifying pts for whom maintenance chemotherapy is effective. [Table: see text]
Somatic mutation in the EGFR gene in ovarian carcinoma detected by SSCP and direct sequencing
Authors: Terai Y. , Sugita M. , Ueda M. , Ueki M. , Bemis L. , Haney J. , Franklin W. A. 
Published: March 2020

5063 Background: Recently, mutations of the EGFR kinase domain have been described in adenocarcinoma of lung and are particularly common in non-smoking females of Japan. These tumors are more responsive to blockade of the EGFR TK domain than non-mutant tumors. Ovarian tumors are known to express EGFR but the frequency of EGFR mutation at this site has not been explored. Methods: We have searched for mutations in the EGFR gene in ovarian carcinoma in two ways, first by single stranded conformation polymorphism (SSCP) analysis of appropriately amplified DNA from microdissected paraffin sections and then by direct forward and reverse sequencing of the DNA for mutations in exons 18, 19 and 21. Results: There was poor correlation between the two methods. By direct sequencing and evaluation of sequence chromatograms by Mutation Surveyor, mutations were detected in 8 of 79 patients (10.1%). Three of the mutations have been previously described in NSCLC including two in-frame deletions in exon 19 (codons 746–750) and one point mutation in exon 21 (L858R). Previously undescribed point mutations resulting in amino substitutions were found in an additional 5 patients including two patients with multiple mutations. These point mutations included 3 in exon 18 (Q701R, L704S and T725A) and 5 in exon 21 (N830G, R832C, T852M, I853V and Q868D). Deletions were detected by SSCP but point mutations were not detected. Conclusions: We conclude that a low but definite frequency of mutation in the EGFR tyrosine kinase domain occurs in ovarian carcinoma in the Japanese population and that these tumors may be targeted by EGFR blockers. SSCP can detect multibase deletions but is an unreliable method for detection of point mutations. No significant financial relationships to disclose.
Evaluation of serial serum IL-6 levels in women with newly diagnosed ovarian cancer on a prospective clinical trial
Authors: Mahoney J. , Lee H. , Foster R. , Matulonis U. , Duan Z. , Seiden M. V. 
Published: March 2020

5065 Background: Elevated levels of IL-6 in serum have been reported in patients (pts) with mullerian malignancies (MM) and have been associated with a poor prognosis. Little is know about the behavior of IL-6 during effective cytotoxic therapy and its correlation to various clinical parameters. Methods: Pts with surgically debulked FIGO Stage II, III, and IV MM were enrolled in the Modified Triple Doublets trial. 83 pts were assigned to a cohort in accordance with the extent of surgical debulking. Cohort I included women who had been optimally cytoreduced to <1cm of residual tumor. Cohort II consisted of pts who had either post-debulking residual disease >1cm or stage IV disease. Both cohorts were treated with 3 sequential chemotherapy doublets, gemcitabine/carboplatin, paclitaxel/carboplatin, and adriamycin/topotecan. Each doublet was delivered for 3 cycles. Serum was collected from pts prior to initiating each doublet at cycles 1, 4, 7 and at the end of study (post cycle 9). Serum IL-6 levels were measured in triplicate by sandwich ELISA. Results: Pts with MM had elevated levels of IL-6 following debulking surgery (mean = 12.7 pg/ml) as compared to normal controls (n = 11, mean IL-6 = 1.5 pg/ml, p =.01). While there was no significant correlation between IL-6 levels and stage of disease, the IL-6 serum concentrations did correlate with extent of surgical debulking (p = 0.0182). IL-6 concentrations dropped throughout all cycles of platinum based treatment with post platinum treatment mean concentration of 3.9pg/ml. IL-6 levels did not correlate with outcome of second look operation and there was no statistically significant correlation between IL-6 and CA-125 levels (p = 0.1612). Survival data is still immature with a median follow-up of 34 months, yet elevation of IL-6 levels following surgery demonstrates a trend towards inferior survival. Conclusions: IL-6 levels are elevated in ovarian cancer pts following surgical debulking and correlate with the volume of residual disease following surgical cytoreduction. Values decrease during cytoreductive platinum based chemotherapy although IL-6 was not as predictive of response as was CA-125. Data demonstrates a weak correlation betweenworse survival and elevated IL-6 levels. Supported by the Lana Vento Foundation. No significant financial relationships to disclose.
Randomized trial of systematic lymphadenectomy (LY) vs nodal sampling (SA) at second look surgery (SLS) in ovarian cancer patients: Final results
Authors: Landoni F. , Maggioni A. , Dell’anna T. , Benedetti Panici P. , Manci N. , Torri V. , Tironi R. , Garcia Parra R. , Falci C. , Fossati R. 
Published: March 2020

5068 Background: The role of systematic pelvic and para-aortic lymphadenectomy at SLS in ovarian cancer patients has not been addressed by randomized clinical trials (RCTs). We conducted a RCT to determine whether LY improves progression-free (PFS) and overall survival (OS) compared with SA. Methods: From January 1991 through December 1999, 303 eligible patients (i.e. patients with FIGO stage I-IV epithelial ovarian carcinoma at up front surgery and in complete remission after primary debulking surgery and first line chemotherapy) were randomly assigned to undergo LY (N = 156) or SA (N = 147) at the end of SLS. Survival was analyzed using a Cox multivariable regression analysis. All statistical tests were two-sided. Results: Median operating time was longer and the percentage of patients requiring blood transfusions was higher in the LY arm than the SA (240 vs 135 min., P < .001, and 30% vs 10%, P < .001, respectively). In the LY arm and SA arm the median number of removed nodes and the percentages of patients with nodal involvement was statistically different (44 vs 8, P < .0001, and 24% vs 13%, P = 0.018, respectively). At a median follow-up of 59 months, 156 events (i.e., recurrences or deaths) were observed, and 98 patients had died. The 5-year progression-free and overall survival was 41% and 65% for LY, 49% and 61% for SA, respectively. The risk for first event (hazard ratio [HR] = 1.11, 95% CI = 0.81 to 1.53; P = .50) and death (HR = 0.79, 95% CI = 0.53 to 1.18; P = .24) after adjustment for residual tumor at first surgery was not significantly different between the two arms. Conclusions: Although LY at SLS seemed to improve overall survival, this survival gain (21% decrease in the hazard of death) was not statistically significant and therefore the routine use of LY at SLS for ovarian cancer is not supported by this RCT. No significant financial relationships to disclose.
The role of extensive lymphadenectomy in stage I ovarian cancer
Authors: Munro E. G. , Karnik Lee N. , Cheung M. K. , Osann K. , Husain A. , Teng N. N. , Kapp D. S. , Berek J. S. , Chan J. K. 
Published: March 2020

5069 Background: To determine if extent of lymphadenectomy affects the survival of women with stage I ovarian cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 6,686 women diagnosed with stage I ovarian cancer, 4,092 (61.2%) had stage IA, 392 (5.9%) had stage IB, 1,840 (27.5%) had stage IC, and 362 (5.4%) had unspecified stage I disease. The median age was 53 (range: 1–99). 5,625 (84.1%) were White, 388 (5.8%) Black, 488 (7.3%) Asian, and 185 (2.8%) were Other. All patients underwent primary surgery; of which, 3,824 women had no nodes, 1,533 had <10 nodes, and 1,329 had ≥10 nodes resected. Of the patients who underwent a lymphadenectomy, the median number of nodes resected was 9 (range: 1–84). The extent of lymphadenectomy (0, <10, and ≥10 nodes) increased the survival of patients with stage IC disease from 72.8%, 86.7%, to 90.1% (p < 0.0001), but not in those with stage IA (p = 0.07) or stage IB (p = 0.04) disease. In patients with non-clear cell epithelial carcinoma, the extent of lymphadenectomy was associated with improved 5-year disease-specific survivals of 85.6%, 93.3%, and 93.5%, respectively (p < 0.0001). However, the benefit associated with an extensive lymphadenectomy was not evident in clear cell (p = 0.09), sarcoma (p = 0.33), germ cell (p = 0.55), or sex cord stromal tumors of the ovary (p = 0.99). Similarly, patients with grade 3 disease had an improved survival associated with the extent of lymph node resection, 74.4%, 87.5%, to 90.5% (p < 0.0001), but not in those with grade 1 (p = 0.18) or grade 2 (p = 0.27) disease. In multivariate analysis, a more extensive lymphadenectomy remained significant as an independent prognostic factor for improved survival after adjusting for all other independent prognostic factors including age, surgery, histology, stage, and grade. Conclusions: Our findings suggest that the extent of lymphadenectomy was associated with an improvement in the survival of women with stage IC ovarian cancer. No significant financial relationships to disclose.
A phase IB, open label, safety and pharmacokinetic (PK) study of escalating doses of PTK787/ZK 222584 (PTK/ZK) in combination with paclitaxel and carboplatin in patients (Pts) with stage IC to IV epithelial ovarian cancer (EOC)
Authors: Schroder W. , Campone M. , Abadie S. , Witteveen P. , Viens P. , Jalava T. , Palacay-Radona M. , Bilic S. , Laurent D. , Du Bois A. 
Published: March 2020

5075 Background: Vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) are important mediators of tumor growth and metastasis and their expression is associated with poor prognosis in EOC. PTK/ZK is a novel, oral, angiogenesis and lymphangiogenesis inhibitor that blocks tyrosine kinase signaling from all known VEGFRs. Methods: An open label, multicenter, phase IB dose escalation study evaluating PTK/ZK with chemotherapy as first line therapy in Pts with stage IC to IV EOC. Maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of PTK/ZK were assessed; PK of PTK/ZK, carboplatin and paclitaxel was characterized. Paclitaxel was administered as a 3-hour infusion on day 1 of each 21-day cycle at a dose of 175 mg/m2. Carboplatin was given immediately after paclitaxel as a 30-min IV infusion to AUC of 5 mg min/mL. PTK/ZK was given once daily from day 3 to day 21 of each chemotherapy cycle. Cohorts of 3 to 6 Pts received doses of PTK/ZK at 250, 500, 750, 1000 or 1250 mg/day. Dose expansion in 21 additional Pts was conducted with 1250 mg/day without reaching MTD. After completion of chemotherapy, PTK/ZK was given continuously until disease progression. PK samples were collected in cycle 1 (without PTK/ZK) and cycle 2 (after PTK/ZK pre-treatment). Results: 42 Pts were enrolled. To date 39 Pts are evaluated for safety, 19 Pts for DLT, 35 Pts for PK and 21 Pts with residual disease for tumor response. No DLTs were reported. The most frequently observed grade 3/4 toxicity was neutropenia (31%), leucopenia (18%) and hypertension (10%). PTK/ZK did not aggravate chemotherapy related side effects. To date 67% of Pts had achieved CR/PR, 9% SD, 5% PD and 19% UNK. PTK/ZK exposure at steady state was similar in cycle 1 and 2. PTK/ZK had no impact on the systemic exposure of carboplatin. Paclitaxel exposure was decreased by an average of 18% in cycle 2 compared to cycle 1 for Pts treated with PTK/ZK 1250 mg/day. Conclusion: Combination of PTK/ZK with paclitaxel and carboplatin is feasible and shows favorable safety profile. The combination is active in EOC and deserves further evaluation. [Table: see text]