bluuebunny/crossref_metadata_2025_split huggingface dataset:
NKTR-102 in patients with platinum-resistant ovarian cancer (PROC): Modeling CA125 response and its correlation with tumor response.
Authors: Chia Yen Lin , Hoch Ute , Leung Abraham C. F. , Eldon Michael A. 
Published: March 2020

5048 Background: NKTR-102 is a unique topoisomerase 1 inhibitor that provides continuous exposure to SN38. In heavily pretreated pts with PROC (median of 3 prior therapies; 27 pts were platinum refractory), 145 mg/m2 NKTR-102 given q14d or q21d demonstrated significant anti-tumor activity (JCO 28:7s, 5013). We present a PK/PD model for CA125 kinetics that can be used to project GCIG response as an aide to selecting dose and schedule. Methods: Data from 55 pts with PROC and elevated CA125 (median baseline = 515 U/mL) were fit with a PK/PD model developed to correlate CA125 dynamics with SN38 conc-time profiles predicted from individual pt dosing history: d[CA125]/dt = Kin*exp(beta*t)*(1-[SN38]/(IC50+[SN38]))-Kout*[CA125]. Results: CA125 profiles were well described by the model, with a population mean SN38 IC50 of 1.1 ng/mL. Typical min and max SN38 conc during treatment were 1.5 and 3 ng/mL for q14d and 0.9 and 2.4 ng/mL for q21d, indicating that both schedules resulted in SN38 exposure near the IC50. The half-life of CA125 decline was 6.4 days, similar to literature values. 46 of 55 pts had pre- and post-treatment tumor measurements for correlation of CA125 response and tumor size. Overall best response by GCIG and RECIST correlated in 57% of pts. 33% of pts with GCIG response showed declines in tumor size, albeit insufficient to classify as RECIST response. 72% of pts with GCIG SD showed at least SD by RECIST. CA125 vs time was simulated for 1000 pts receiving 145 mg/m2 NKTR-102 q14d or q21d, to allow comparison of CA125 and GCIG response between schedules (see table). The % pts per GCIG response was comparable between schedules, supporting use of the better-tolerated q21d regimen. Conclusions: The PK/PD model described CA125 profiles well, providing a tool to predict drug response from SN38 PK data. Close correlation of CA125 with tumor size is consistent with historical use of CA125 as a surrogate marker. Predicted CA125 profiles for NKTR-102 q14d or q21d were similar, suggesting that the better-tolerated q21d schedule will produce results consistent with those from Ph 2. [Table: see text]
Effect of tumor-infiltrating T-lymphocytes on the aggressiveness of epithelial ovarian tumors.
Authors: Vasconcelos Ines , Olek Sven , Gellhaus Katharina , Schwachula Tim , Braicu Ioana , Fotopoulou Christina , Chekerov Radoslav , Dimitrova Desislava , Sehouli Jalid 
Published: March 2020

5053 Background: Borderline ovarian tumors (BOT) are a low-grade form of ovarian malignancy with significantly less aggressive behavior than epithelial ovarian cancer (EOC). Since there is neither convincing scientific evidence nor a marker capable of predicting BOT’s behavior, we analyzed the role of immune tolerance in differential disease outcome. EOC and BOT were chosen due to similar disease etiology, despite different disease courses. Increased numbers of T-cell subpopulations infiltrate malignant tumors, so we used epigenetic tests to determine the prevalence of regulatory T-cells (Treg) and overall-T-Lymphocytes (oTL) in EOC and BOT. Methods: The ovarian cancer samples were provided by the European multicentric OVCAD study. The BOT samples were obtained from Tumor Bank Ovarian Cancer at Charité Campus Virchow (Germany). Samples and clinical data were prospectively collected and documented using validated SOPs. DNA was bisulphite-converted and forwarded to methylation-specific RT-PCR for CD3 and FOXP3 loci. Results: We evaluated 90 high-grade EOC, 12 BOT with invasive implants and 25 non-invasive BOT samples. Higher oTL-values correlate with mortality (p=0.008) and recurrence (p<0.001), while higher Treg levels correlate with recurrence (p=0.028). Patients with non-invasive BOT have lower oTL (p=0.019) and Treg (p=0.0005) levels than patients with invasive BOT and EOC, while BOT (both invasive and non-invasive) patients have lower Treg-to-oTL ratios than EOC patients (p=0.0005). Finally, oTL levels associate with overall survival in EOC (p=0.042). Conclusions: We observed a strict correlation between tumor-type, Treg and oTL levels, as well as Treg-to-oTL ratio. This is in agreement with our hypothesis that disease aggressiveness is associated with the amount tumor-infiltrating lymphocytes and may provide the explanation for differing disease courses in EOC and BOT.
Treatment reality in elderly patients with advanced ovarian cancer: A prospective analysis of the OVCAD consortium.
Authors: Woelber Linn Lena , Eulenburg Christine , Braicu Ioana , Sehouli Jalid , Lambrechts Sandrina , Vergote Ignace B. , Hager Gudrun , Zeillinger Robert , Zeimet Alain G , Mahner Sven 
Published: March 2020

5058 Background: Approximately one third of women diagnosed with ovarian cancer are 70 years or older. Standard therapy of ovarian cancer including radical cytoreduction and combination chemotherapy has considerable morbidity and information regarding treatment reality in elderly patients with ovarian cancer is very limited. Methods: Patients with primary epithelial ovarian cancer FIGO-stages IIB-IV were prospectively included in 5 European cancer centers. All patients underwent surgery with the intent of maximal cytoreduction and platinum-based chemotherapy. To analyze treatment strategies and outcome in the elderly, patients were subdivided in <70 years and ≥70 years of age and compared regarding clinicopathological variables and prognosis. Results: A total of 275 patients were included and followed for a median of 25 months. Median age of the total cohort was 58 (18-85) years with only 47 patients (17.1%) ≥70 years old. Age itself was not a prognostic factor for progression free survival (PFS) in multivariate analysis. 30-days mortality rate after primary surgery was 3.6% in elderly patients compared to 0.6% in patients <70 years (p=0.153). Surgery was less radical in patients ≥70 (e.g. fewer lymph node dissections p<0.001) and the percentage of patients with residual disease after surgery was higher in elderly (44.7%) compared to younger patients (28.5%) despite similar FIGO stage distribution (p=0.029). Furthermore, elderly received more often mono-chemotherapy (p<0.001). Consequently, outcome was less favorable in patients ≥70 compared to patients <70 years (75% overall survival 16 vs. 28 months; p=0.002 and median PFS 14 vs. 20 months; p=0.182). Conclusions: In this prospective European multicenter study, ovarian cancer patients age 70 and older were treated significantly less radical and had unfavorable outcome compared to younger patients. Specific trials for elderly patients focusing on surgical as well as chemotherapeutic aspects are therefore highly desirable to gain more information in an aging society.
Factors associated with an increased risk of recurrence in women with ovarian granulosa cell tumors.
Authors: Suri Anuj , Horowitz Neil S. , Carter Ebony B. , Denslow Sheri , Gehrig Paola A. 
Published: March 2020

5063 Background: There is emerging data in different malignancies, including gynecologic cancers, demonstrating factors independent of a patient’s tumor characteristics, which are associated with an increased risk of cancer recurrence. The goal of this study is to determine demographic and prognostic factors affecting recurrence of disease (RD) in women with ovarian granulosa cell tumors (GCT). Methods: A dual-institution retrospective analysis of patients diagnosed with GCT between 1995 and 2010. Demographics including age, race, BMI, stage, diabetes (DM), adjuvant treatment, and progression free survival (PFS) were extracted. Hazard ratios for recurrence were estimated by univariate and multivariate Cox regression models Results: One hundred nine women identified with a median age of 50 (range 12-87). Fifty-six (57.1%) were Caucasian, 32 (32.7%) African American, and 10 (10.2%) were other. Median BMI was 29 (range 12-57). Twenty-one patients had DM. The majority of women had stage I disease (89.0%), 7 (6.4%) had stage II/III disease, and 5 were unstaged. In univariate analysis, DM showed the strongest association with recurrence (HR 3.56, 95% CI: 1.57-8.11). Non-white race was also associated with higher risk of RD, though the association was not statistically significant (HR 1.74, 95% CI: 0.78-3.87). The association between DM and RD was also found in multivariate analysis controlling for all factors including non-white race and BMI (HR 2.99, 95% CI: 1.11-8.08). Only 19 (17%) patients received adjuvant chemotherapy consisting of one of two different adjuvant chemotherapy regimens bleomycin, etoposide, and cisplatin or paclitaxel and carboplatin, however there was no difference in outcome based on chemotherapy regimen (p=0.24). Conclusions: This is the largest study analyzing factors associated with risk of recurrence in women with ovarian GCT. Studies have demonstrated higher morbidity among diabetic patients with breast and colon cancer and this may be modifiable with metformin. Our results emphasize that diabetes is one of the strongest predictors of recurrent disease in patients with ovarian GCT. Further studies are necessary to evaluate the effect of other factors such as adjuvant chemotherapy.
Interval versus primary tumor debulking surgery in advanced ovarian cancer: Analysis of the European OVCAD data.
Authors: Fotopoulou Christina , Braicu Ioana , Vergote Ignace B. , Cadron Isabelle , Amant Frederic , Chekerov Radoslav , Castillo-Tong Dan Cacsire , Speiser Paul , Richter Rolf , Concin Nicole , Marth Christian , Mahner Sven , Trillsch Fabian , Zeillinger Robert , Sehouli Jalid 
Published: March 2020

5071 Background: The international scenery around optimal primary treatment of advanced ovarian cancer (AOC) patients (pts) is currently being discussed, with large discrepancies and heterogeneity still existing between the national guidelines worldwide. Aim of the present study was to evaluate the differences in outcome of AOC-pts after primary (PDS) versus interval-debulking-surgery (IDS) based on a prospectively assessed multicenter data set. Methods: Overall outcome was analyzed from the OVCAD database; a prospective, observational, multicenter project. AOC-pts who underwent surgery in five specialized gynecological cancer centers across three European countries between 02/2005 and 12/2008 were evaluated. Overall (OS) and progression free survival (PFS) were calculated by Kaplan-Meier-curves. Univariate and Cox-regression-analysis were applied. Results: Overall, 256 AOC pts (FIGO-stage III/IV) were evaluated. Fifty pts (19.5%) underwent IDS and 206 pts (80.5%) PDS. Despite the non-randomized setting both groups were well balanced in terms of FIGO-stage, grading, histological subtype and presence of ascites. Different selection criteria were however present for each center. PDS pts presented significantly higher rates of intestinal resection (44.2% vs.24%; p=0.01) and lymphonodectomy compared to IDS ones (72.3%vs.48%; p=0.001), by equivalent complete tumor resection rates (67.5% vs.68%; p=0.82). Platinum response was significantly higher in PDS vs. IDS pts (80.6% vs. 54%; p<0.001). 3-years OS was with 66.7% (95%CI: 60.2-73.2%) significantly better in PDS- versus 48.3% (95%CI: 34.2-62.5%) in IDS pts (p<0.001). Also 2-years PFS was with 31.9% (95%CI:24.8-39.1%) significantly higher in PDS- vs. 11.4% (95%CI: 0.9-22%) in IDS-pts (p<0.001). In multivariate analysis PDS, but not age, ascites, FIGO-stage, grading, histology or residual tumor were of prognostic significance for platinum response. In addition, multivariate analysis identified PDS and no residual tumor to positively and ascites to negatively affect OS and PFS. Conclusions: PDS appears to be associated with a more favorable outcome compared to IDS in highly specialized centers according to this non-randomized data set.
Exposure-response relationship of open-label (OL) AMG 386 monotherapy in patients (pts) with recurrent ovarian cancer.
Authors: Karlan Beth , Lu Jianfeng , Navale Lynn , Rasmussen Erik , Sun Yu-Nien , Vergote Ignace B. , Kuchimanchi Mita , Warner Douglas , Weinreich David M. 
Published: March 2020

5072 Background: AMG 386, an investigational peptibody, inhibits tumor angiogenesis by preventing angiopoietins 1/2 and Tie2 receptor interaction. A phase II, double-blind, controlled study (NCT00479817) evaluated toxicity and efficacy of AMG 386 + paclitaxel (P) in recurrent ovarian cancer pts. Increased AMG 386 exposure in that study was associated with longer progression-free survival (PFS; Lu et al., JCO 2010; 28 [Suppl]: 5042). Here, these analyses were applied to pts electing OL AMG 386 monotherapy after progression in the placebo group. Methods: Pts with recurrent epithelial ovarian, fallopian tube, or peritoneal cancer (≤3 prior anticancer therapies, GOG ≤1) were randomized 1:1:1 to P IV QW (3 on/1 off) + AMG 386 (3 or 10 mg/kg) or placebo IV QW. In the placebo group, pts who progressed and stayed eligible could receive OL AMG 386 10 mg/kg IV QW monotherapy. In pts receiving AMG 386 monotherapy, post-hoc analyses evaluated PFS per RECIST, objective response rate (ORR), adverse events (AEs), and the relationships between high and low AMG 386 exposure (based on a median AUCSS of 10.6 mg*hr/mL) and efficacy (PFS per RECIST, ORR). Results: 161 pts were randomized. 18 pts received OL AMG 386 monotherapy (range: 1-56 infusions). At the time of analysis, PFS was 3.2 mo. ORR was 0%. 6 pts had stable disease (SD), 7 had progressive disease (PD). Common AEs were abdominal pain (n = 6), fatigue (n = 5), peripheral edema (n = 5), nausea (n = 5), urinary tract infection (n = 5), and vomiting (n = 5); grade ≥ 3 AEs in more than 1 pt were pleural effusion (n = 2; all grade 3), small intestinal obstruction (n = 2; all grade 3), and ovarian cancer (n = 2; all grade 5). PFS was longer in the high- (n = 9) vs low-exposure (n = 9) group (7.2 vs 1.8 mo; HR = .266, p = .041). Precrossover PFS was similar between high- and low-exposure groups (5.5 vs 4.5 mo; HR = 1.146, p = .812). For both groups, ORR was 0%. In the high-exposure group, 4 pts had SD, 3 had PD. In the low-exposure group, 2 pts had SD, 4 had PD. Conclusions: In line with results from a phase II study of AMG 386 + P, pts with recurrent ovarian cancer who received AMG 386 monotherapy and had high AMG 386 exposure had longer PFS than pts with low exposure. Toxicity was similar in both groups.
A matched pair analysis of intra- and postoperative catumaxomab in patients with ovarian cancer from a multicenter, single-arm phase II trial versus a consecutive single-center collective of ovarian cancer patients without immunotherapy.
Authors: Pietzner Klaus , Chekerov Radoslav , Reinthaller Alexander , Reimer Daniel , Reimer Toralf , Angleitner-Boubenizek Lukas , Tschirschmann Miriam , Lindhofer Horst , Braicu Elena Ioana , Fotopoulou Christina , Sehouli Jalid 
Published: March 2020

5080 Background: Advanced ovarian cancer is still connected to high mortality rates due to intraperitoneal tumor cells that survive radical cytoreductive surgery as well as adjuvant chemotherapy. These persistent tumor cells need to be targeted in order to improve survival. Catumaxomab has demonstrated the ability to kill EpCAM-positive intraperitoneal tumor cells of ovarian cancer patients in studies aiming to controll malignant ascites in the recurrent setting. This analysis was conducted to investigate the efficacy of intraperitoneal catumaxomab at the timepoint of primary cytoreductive surgery and postoperative period, prior to standard adjuvant chemotherapy. Methods: Ovarian cancer patients undergoing radical surgery received one intraoperative (10 μg) followed by four subsequent intraperitoneal (i.p.) dosages (10, 20, 50 and 150 μg) of catumaxomab on days 7, 10, 13, and 16, respectively. Because of the single arm design of the study, the patients treated with catumaxomab were compared in a matched pair analysis to consecutive patients with primary ovarian cancer who received standard treatment without catumaxomab in a large center, in order to compare survival. The two main prognostic factors of stage and level of tumorreduction were chosen as matching criteria. Results: Of 58 patients screened, 41 were treated with catumaxomab and available for survival evaluation. Median age was 57 years in the catumaxomab group and 59 years in the matched-pair control group. The most comon histology was the serous subtype with 70.7 % in the catumaxomab and 80.5 % of the patients in the control group. The median for overall survival was reached for the historical consecutive matched-pair control collective, but is not yet reached for the catumaxomab group. However, 3-year survival data were available for both groups and showed survival of 85.4% (35) in the catumaxomab group and 63.4% (26) in the matched-pair control group (p-value: 0.041; HR 2.073) Conclusions: There seems to be a trend to beneficial 3-year survival in the catumaxomab group, suggesting that a phase III trial is warranted.
Final results of a phase II trial of weekly nab-paclitaxel with GM-CSF as chemoimmunotherapy for platinum-resistant epithelial ovarian cancer.
Authors: Swensen Ron E. , Goff Barbara Ann , Childs Jennifer , Higgins Doreen , Gooley Theodore , Fintak Patricia A , Buening Barbara , Disis Mary L. 
Published: March 2020

5082^ Background: Ovarian cancer patients with an anti-tumor immune response have a prolonged survival, suggesting that augmenting anti-tumor immunity may be therapeutic. We hypothesized that weekly nab paclitaxel (nabP) followed by GM-CSF may enhance anti tumor immunity and prolong time to progression (TTP). Methods: Eligible subjects had platinum resistant ovarian, primary peritoneal or fallopian tube cancer, and an elevated CA125. Conditional power estimate after 11 subjects showed 22 subjects had 80% power to show a response rate (RR) >21% if the true study RR is 35%. Study end points were RR and TTP. Progression (DP) was doubling of CA125 above the nadir. Complete response (CR) was a decline of CA125 below institutional normal. Partial response (PR) was a decline of >50% from baseline. Stable disease (SD) was all other scenarios. Subjects received nabP, 100mg/m2 days 1,8,15 followed by GM-CSF 250mcg days 16-26 of a 28 day cycle until progression or 6 cycles were complete. Responding subjects received up to 6 more cycles of GM-CSF on days 14-28. Results: 21 subjects received at least one dose of study medications. Median age was 61 (30-91) and had a median of 3 (1-13) prior regimens. Among those completing the study, the median TTP was 132 days vs. 272 days on the prior platinum regimen. 9/21 (43%) had a PR and 4/21 (19%) had a CR. Subjects with a response had a median TTP of 140 days. Assay of serial T-lymphocyte counts against CEA, MUC1, CA125 and tt and influenza controls are planned. Conclusions: Weekly nabP with GM-CSF had manageable toxicity and induced a high response rate (62% by CA125) in patients with platinum resistant ovarian cancer, however this regimen did not prolong the TTP beyond the TTP observed in the prior platinum regimen.
Prospective multicenter study evaluating the survival of patients with locally advanced cervical cancer (LACC) and negative positron emission tomography with computerized tomography (PET-CT) in the para-aortic area undergoing laparoscopic para-aortic (PA) lymphadenectomy before chemoradiation therapy.
Authors: Gouy Sebastien , Morice Philippe , Narducci Fabrice , Uzan Catherine , Rey Annie , Martinez Alejandra , Pautier Patricia , Deandreis Desiree , Querleu Denis , Haie-Meder Christine , Leblanc Eric 
Published: March 2020

5083 Background: In three comprehensive cancer centers, patients with LACC were systematically staged using conventional and PET-CT imaging before chemoradiotherapy. If patients had no uptake in the PA area, laparoscopic extraperitoneal PA surgery was then performed to define radiation field limits more accurately. The aim of this study was to evaluate the therapeutic impact of this management. Methods: A prospective multicenter series of 237 patients treated from 2004 to 2011 for LACC with a negative PET-CT of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous between Institutions. Patients with a poor prognosis histologic subtype, peritoneal carcinomatosis or ovarian metastasis were excluded. Results: Clinical stages were IB2 (n=79), IIA (n=10), IIB (n=120), III (n=23), IVA (n=5). The histologic types were squamous carcinoma (n=197), adenocarcinoma (n=34) and others (n=6). Twenty-nine (11%) patients had nodal involvement (false negative PET-CT results): 16 with PA nodal metastasis measuring > 5 mm and 13 < 5 mm. With a median follow-up of 18 (range, 0-67) months, disease-free survival (DFS) at 2 years in patients without and with PA involvement was respectively 76% (68%-83%) and 61% (37%-80%)(p=.007). DFS at 2 years in patients without PA involvement or with PA metastasis measuring < or > 5 mm was respectively 76% (68%-83%), 89% (57%-98%) and 38% (14%-68%)(p=.0006). Conclusions: This is the largest series of patients reported undergoing such strategy. We obtained a similar survival rate for patients with PA nodal metastasis < 5 mm and patients without PA lymph node involvement suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement > 5 mm remained poor, despite no extrapelvic disease at PET-CT imaging in this subgroup. Other treatment modalities should be evaluated for these patients.
The impact of racial disparity on outcomes of patients with early-stage uterine endometrioid carcinoma in an equal-access environment.
Authors: Robbins Jared R. , Laser Benjamin S. , Bhat Neal , Cogan Chad , Munkarah Adnan , Elshaikh Mohamed A. 
Published: March 2020

5088 Background: To determine if racial disparity exists between African American (AA) and non-African American (NAA) patients with early stage uterine endometrioid carcinoma who had similar multidisciplinary management. Methods: Our prospectively-maintained database of 1,450 uterine cancer patients was reviewed for this IRB-approved study. We identified 766 consecutive patients with endometrioid carcinoma 1988 FIGO stages I-II who underwent hysterectomy between 1987-2009. Patients with non-endometrioid carcinoma, mixed histologies and those who received preoperative treatments were excluded. For the purpose of data analysis, patients were divided into two groups; AA and NAA. Recurrence-free survival (RFS), disease specific (DSS) and overall survival (OS) was calculated from the date of hysterectomy using the Kaplan-Meier method. Cox regression modeling was used to explore the risks of various factors on recurrence. Results: Median follow-up was 5.1 years. 27% were AA and 73% were NAA. All patients underwent hysterectomy and oophorectomy. 80% had peritoneal cytology and 69% underwent lymphadenectomy. AA patients were more likely to have higher grade tumors, and more lymphovascular space involvement (LVSI). Although the two groups were balanced in regards to surgical staging and adjuvant treatment received, the five-year RFS and DSS were significantly lower in AA compared to NAA patients (91% vs 84%, p=0.030; 95% vs 88%, p=0.011, respectively). Between the two groups, OS was not significantly different. On multivariate analysis and after adjusting for other prognostic factors, race (AA vs NAA) was not a significant predictor of outcome. Grade 3 tumors and the presence of LVSI were the only two independent predictors of RFS and DSS with p=<0.001 and p=<0.001, respectively. Conclusions: In this large hospital-based study, AA race was associated with a higher incidence of adverse pathological features and worse recurrence-free and disease-specific survival. However, on multivariate analysis race was not an independent prognostic factor. Further studies are needed to elucidate possible underlying molecular mechanisms for these poorer outcomes.