bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab (Bev) for treatment of recurrent serous borderline (SB) or low-grade serous (LGS) ovarian cancer: A retrospective review of the Memorial Sloan-Kettering Cancer Center (MSKCC) experience.
Authors: Grisham Rachel N. , Sala Evis , Zhou Qin , Iasonos Alexia , DeLair Deborah , Iyer Gopa , Hyman David Michael , Spriggs David R. , Aghajanian Carol 
Published: March 2020

5545 Background: LGS ovarian cancer is a rare subtype of ovarian cancer, accounting for 10% of ovarian cancer cases. Patients typically present at an early age, exhibit a protracted clinical course, and have response rates to chemotherapy of < 4%. Limited clinical data suggests that bev may have activity in this disease. The objective of this study was to determine the response rate to treatment with bev in patients with SB or LGS ovarian cancer treated at MSKCC. Methods: Following IRB approval, all patients with a diagnosis of SB or LGS ovarian or primary peritoneal cancer treated with ≥ 1 dose of bev for persistent or recurrent disease were identified. 17 patients were treated at MSKCC between July 2005 and June 2012. Diagnosis was confirmed by a gynecologic pathologist. All imaging was independently reviewed by the study radiologist and response was determined by RECIST 1.1 criteria. Results: 17 patients, 10 with LGS ovarian cancer, 3 with LGS primary peritoneal cancer, and 4 with SB disease were included in the analysis. The mean number of prior therapies was 3.4 (range: 1-9, median: 2). Two patients were treated with bev alone, the remainder (15) received bev in combination with paclitaxel (Pac, 6), topotecan (1), pemetrexed (1), oral cyclophosphamide (3), gemcitabine (Gem, 2), Gem and carboplatin (Carbo) (1), or Pac and Carbo (1) .Two patients were not evaluable for response due to termination of treatment prior to first radiographic assessment. The median duration of bev treatment was 23 weeks (mean: 32.2; range 6-79.4). Conclusions: This data suggests that the addition of bev to cytotoxic chemotherapy may produce dramatically higher response rates than chemotherapy alone in patients with SB and LGS ovarian cancer. A prospective study of bev for treatment of this chemotherapy resistant disease is warranted. [Table: see text]
The role of CHFR expression in ovarian cancer and response to taxane therapy.
Authors: Wahner Hendrickson Andrea Elisabeth , Visscher Daniel W. , Goergen Krista M. , Negron Vivian , Lingle Wilma L. , Oberg Ann L. , Kalli Kimberly , Hartmann Lynn C. , Maurer Matthew J. , Kaufmann Scott H. 
Published: March 2020

5546 Background: CHFR, an E3 ubiquitin ligase that regulates Aurora A and Pololike Kinase 1, plays a critical role in the cellular response to mitotic stress. In particular, cells containing CHFR arrest in G2 when microtubule dynamics are disrupted. Conversely, low CHFR expression is associated with hypersensitivity to mitotic spindle poisons in breast cancer cell lines. Despite the extensive use of taxanes in front line treatment of epithelial ovarian cancer (EOC), little is known about CHFR expression in this disease. We examined CHFR expression and its relationship with clinical characteristics and outcome in women with EOC. Methods: Pretreatment EOC samples from women enrolled in the Mayo Clinic Biospecimen Resource for Ovarian Cancer Research who underwent initial surgical debulking between 1999-2009 were stained in triplicate with anti-CHFR antibodies. Samples were scored in a blinded fashion for CHFR expression. Associations between CHFR staining and histology, grade, and stage were assessed using chi-squared tests; associations between CHFR and overall survival (OS) or time to disease recurrence (TTR) were assessed using Cox proportional hazards models. Results: Samples from 354 women were stained; median age at diagnosis was 60.5 (range 21-93). At a median follow-up of 67 months, 221 women (62%) had died. Across all patients, moderate/strong CHFR staining was associated with poor OS (HR = 1.39, 95% CI: 1.07-1.81, p = 0.015). Moreover, moderate/strong CHFR expression was strongly associated with serous histology (p < 0.0001), high grade (p < 0.0001) and advanced stage (p = 0.0002). To assess whether the association between CHFR expression and OS was related to taxane sensitivity, a subgroup analysis was performed in the subset of patients (N=131) with high-grade serous EOC who received initial platinum/taxane chemotherapy. Moderate/strong CHFR expression failed to correlate with OS (HR=0.91, 95% CI: 0.57-1.45, p = 0.68) or TTR from the start of chemotherapy (HR = 0.85, 95% CI: 0.55-1.31, p = 0.55) in this subset. Conclusions: CHFR expression is associated with poor OS and adverse clinical characteristics in patients with EOC but does not appear to be related to taxane sensitivity in high-grade serous tumors.
Analysis of clinical features of ovarian cancer (OC) and breast cancer (BC) among BRCA-mutated (BRCA+) and sporadic (NH) double tumours.
Authors: Nicoletto Maria Ornella , Rocchetto Marco , Artioli Grazia , Perin Alessandra , Ghiotto Cristina , Borgato Lucia , Fiduccia Pasquale , Dalla Palma Maurizia , Koussis Haralabos , Zustovich Fable , Ercoli Alfredo , Litta Pietro , Nardelli Giovanni B. , Zagonel Vittorina 
Published: March 2020

5548 Background: The clinical outcome of double OC and BC is specifically unknown either BRCA+ and in double tumours NH patients. Methods: The present databases made of 106 patients, 67 cases of NH (negative, no-tested or ongoing test for BRCA1/2 mutations) and 39 of BRCA+, were constituted to identify the clinical and pathological features of BC and OC. The primary endpoint was to evaluate biological characteristics of both cancers and clinical outcome of OC in coexistence with BC. Patients were censored at last follow-up or death (any cause) for determination of overall survival (OS). OS were determined using the Kaplan-Meier method and log-rank test to compared the different levels of a variable. Pearson Chi-Square or Fisher’s exact test were used to compare relationship between variables in to groups and Mann-Whitney U test to compare the medians. Results: 32/39 (82 %) BRCA+ and 44/67 (66 %) NH had BC as their first malignancy. As regards the genetic test on NH patients, 28 were BRCA negative, 22 have not been tested and in 10 patients the test is still in progress. All BRCA2 patients had BC as first malignancy, while 20/22 of BRCA1. Bilateral BC was more frequent in BRCA+ than in NH (33 % vs 9 %), resulted in a fivefold higher risk (p = 0.002). III-IV stage OC at diagnosis was 79% in BRCA+ vs 55 % in NH (p = 0.013); indeed BRCA+ patients have a threefold higher risk (however moderate) to develop an advanced stage OC. Death for progression of ovarian cancer involved both groups, and third neoplasm was involved in death cause in 1/1 of BRCA and 5/6 of NH. Two BRCA1 with OC as first neoplasm are alive. Conclusions: III-IV stage OC is more frequent in BRCA+ than in NH, and the main cause of disease progression and death is due to OC. Eventually the most relevant conclusive assessment is the suggestion of a more conserving management for BC and an intensive follow-up for OC in patients with double tumours, irrespective of their pathological or genetic features. Prospective trials are also indicated.
A prognostic factor (PF) index for overall survival in a HER2-negative endocrine-resistant metastatic breast cancer (MBC) population: Analysis from the ATHENA trial.
Authors: Llombart-Cussac Antonio , Pivot Xavier B. , Biganzoli Laura , Cortes-Funes Hernan , Pritchard Kathleen I. , Pierga Jean-Yves , Smith Ian E. , Thomssen Christoph , Palacios Gemma , Srock Stefanie , Sampayo Miguel , Cortes Javier 
Published: March 2020

555 Background: Chemotherapy is the standard of care for patients (pts) with HER2-negative endocrine-resistant MBC. The considerable variability in overall survival (OS) within this population relates essentially to prognostic factors (PF). Increasingly, large studies based on progression-free survival (PFS) as a primary endpoint are now being questioned. An accurate PF index may help in designing innovative trials with appropriate pts selection according to overall survival (OS) prognosis. Methods: The ATHENA trial assessed the safety of first-line bevacizumab combined with non-anthracycline-containing therapy in 2264 pts treated in 37 countries from 2006 to 2009. Pt characteristics, safety, and efficacy have been reported [Breast Cancer Res Treat 2011;130:133-43]. Sixty-one HER2-positive pts were excluded. A multivariate Cox regression model selected PF generating a simple PF index. Of note, skin, lymph node, ipsi-/contra- breast, or other soft tissue involvement was scored as a single organ. Results: After a median follow-up of 20.1 months and 1171 OS events (53% of pts), median OS for the entire sample and triple-negative (TNBC) and non-TNBC subgroups was 25.2 (95% CI 23.9–26.3), 18.3 (16.3–19.7) and 27.3 (26.3–29.3) months, respectively. PF most closely associated with poorer OS were: liver mets or >2 involved organs (HR 1.6; 95% CI 1.5–1.8); DFI ≤24 months (HR 1.7; 1.5–2.0); adjuvant anthracyline and/or taxane (HR 1.1; 1.2–1.4); and TNBC (HR 1.6; 1.4–1.8). A predictive model was designed stratifying by number of PF present (0/1 vs 2 vs 3/4). The model was consistent in both TNBC and non-TNBC populations (Table). Conclusions: A PF index may estimate figures and balance arms in future trials considering OS as primary objective. A well-defined group of non-TNBC accounting for 37% of patients has an OS estimate similar to the most aggressive TNBC. [Table: see text]
Polyvalent vaccine-KLH conjugate and OPT-821 with bevacizumab (BEV) in patients with ovarian cancer in second or greater remission.
Authors: O'Cearbhaill Roisin Eilish , Iasonos Alexia , Zhou Qin , Durany Robert , Aghajanian Carol , Hensley Martee Leigh , Konner Jason A. , Makker Vicky , Tew William P. , Fleisher Martin , Sabbatini Paul 
Published: March 2020

5550 Background: We previously completed a phase I study of a polyvalent vaccine containing GM2, Globo-H, LeY, Tn-MUC1, Tn(c), STn(c) and TF(c) antigens (AGs) individually conjugated to KLH and mixed with adjuvant OPT-821. We showed safe induction of antibody (ab) responses to 5 of the 7 vaccine AGs. Data has shown that tumor vaccine efficacy may be enhanced through disruption of angiogenesis thus providing a rationale for combining BEV with the polyvalent vaccine. We conducted an IRB-approved pilot study to evaluate the safety and immunogenicity of the poly-KLH-vaccine when given with BEV in OC in remission. Methods: Pts with recurrent OC in ≥2nd complete or partial remission were enrolled from 12/2010-03/2012. Pts received 6 vaccines and BEV over 17 weeks. BEV was continued beyond the vaccination phase. Treatment was continued until disease progression or toxicity. Serologic IgM and IgG responses were measured by ELISA against each AG. Wilcoxon signed rank test was used to test changes in cytokines (CKs): FGFβ, IL-8, PDGF, VEGF measured by angio multiplex assay. Results: n=21 Median age 56yrs (51-70). 2, 8, 8, 3 pts were in 2nd, 3rd, 4th, 5th remission, respectively. 1 DLT (gr 4 fever post vaccine #2). Immune Results: n=19 IgG +/or IgM: ≥3 AGs in 17pts. IgM: ≥1 AG in 19pts, ≥3 AGs in 15pts. IgG: ≥1 AG in 17pts, ≥3 AGs in 3pts. CK Results: In 10 pts who completed 6 vaccines there was a mean (median) decrease in VEGF of 144 (111) pg/ml at the 17-week timepoint compared to baseline (p=0.05). For 8 pts who did not complete all 6 vaccines there was a mean (median) increase of 76 (69) pg/ml compared to baseline at the off-study visit (p=0.16). There was no statistically significant change in the other CKs compared to baseline values. At last follow-up, 18 pts had recurred and 3 pts had died. The median PFS was 5.6mths. Conclusions: 89% of pts responded to ≥3 AGs comparable to the 89% response in our prior phase I trial without BEV. BEV and polyvalent-KLH vaccine can be safely administered together with retention of the vaccine’s immunogenicity. Serum VEGF levels decreased in patients on continued BEV therapy. Clinical trial information: NCT01223235. [Table: see text]
A phase II study of oral metronomic combination therapy in relapsed epithelial ovarian cancer.
Authors: Gupta Sudeep , Goyal Gautam , Ghosh Jaya , Bhosale Bharatsinha Baburao , Bajpai Jyoti , Maheshwari Amita , Kerkar Rajendra , Deodhar Kedar , Rekhi Bharat , Menon Santosh , Banavali Shripad 
Published: March 2020

5554 Background: Etoposide (E), cyclophosphamide (C) and tamoxifen (T) have been used as single agents in relapsed epithelial ovarian cancer (EOC) patients. We tested a low dose, continuous, daily, oral metronomic regimen that combined these 3 agents. Methods: This single centre prospective study included patients of relapsed EOC with exposure to at least 2 prior lines of chemotherapy (CT) and at least partial as the best response to most recent regimen. Study regimen comprised daily oral administration of E (50 mg/m2) and C (50 mg/m2) for 21 of a 28 day cycle plus T (20 mg/m2, twice per day) continuously. The primary endpoint was serological (CA-125) progression-free survival (PFS) as per Rustin Criteria and secondary endpoints were radiological (RECIST) PFS, overall survival (OS), duration of response (DOR), response rates and toxicity. The data cut-off date was 15 Jan 2013. Results: 26 patients with a median age of 48 years were accrued, of whom 21 had received 2 prior lines of CT and 5 had received 3 lines. 25 patients who were evaluable for analysis received a median of 6 (1-19) cycles of metronomic regimen. The median delivered relative dose intensities of E, C and T were 0.71, 0.71 and 0.97 respectively. 13 (52%) patients needed dose reduction after a median of 3 (1-9) cycles. Most common grade 3 or 4 toxicities included anemia, neutropenia, febrile neutropenia, nausea, vomiting and diarrhea in 44%, 36%, 12%, 16%, 16% and 12% patients respectively. 19 (76%) patients had serological CR or PR with a median time to response (TTR) and DOR of 1.8 (0.83-2.96) and 7.0 (95% CI, 5.8-8.2) months respectively. 11 (45.8%) of the 24 evaluable patients achieved radiological CR or PR with median TTR and DOR of 3.7 (1.8-7.2) and 5.5 (95% CI, 3.9-7.2) months respectively. 17, 18 and 7 patients have respectively experienced serological progression, radiological progression and death at the time of analysis. The median serological PFS, radiological PFS and OS are 7.9 (95% CI 7.2-8.6), 7.97 (95% CI, 5.95-9.98) and 22.3 (95% CI, 17.4-27.3) months, respectively. Conclusions: The oral metronomic combination of E, C and T has substantial and durable activity in relapsed EOC and is worthy of further evaluation in a larger randomized study.
Does aggressive primary debulking surgery influence survival in ovarian cancer?
Authors: Segev Yakir , Rosen Barry , Murphy Joan , Laframboise Stephane , Dodge Jason Esli , Ferguson Sarah E , Bernardini Marcus , Charles Brendan , Sun Ping , Narod Steven 
Published: March 2020

5561 Background: Evidence comparing outcomes in patients receiving primary debulking surgery (PDS) to those receiving neoadjuvant chemotherapy (NACT) for advanced stage ovarian carcinoma is conflicting. We conducted a retrospective survival analysis of all patients with stage IIIC and IV serous ovarian cancer treated at our institute by either PDS or NACT. Methods: Data was extracted from patient synoptic OR reports and medical records between January 2003 and December 2011. Survival comparisons between patients receiving NACT and PDS were made according to aggressiveness of surgery and residual disease following surgery. Aggressive surgery was defined by one of the following procedures; pelvic peritonectomy, any bowel resection, diaphragm resection, diaphragm peritonectomy and splenectomy. Results: Out of 342 patients, 143 (41%) had NACT and 199 (59%) had PDS. Patients undergoing PDS had a median survival (MS) of 58 months compared to 34 months for NACT. Patients undergoing PDS with > 10mm and <10mm residual disease, had a MS of 33 and 55 months, respectively; whereas those with microscopic disease have not yet reached their MS. In the NACT group, MS for < and > 10 mm residual disease was 30 months for both, compared with 39 months for those with microscopic disease. Within the PDS group, those undergoing limited surgery had a MS of 48 months whereas MS has not been reached for those undergoing aggressive surgery. Over 60% of patients undergoing PDS with microscopic residual were alive at 7 years. In the NACT group, there was no difference in survival according to extent of surgery. Conclusions: Patients withPDS, whether debulked to < 10mm or to microscopic disease have a significant and lengthy survival advantage over patients receiving NACT.
Continuous low-flow ascites drainage and sequential non-invasive tumor-cell sampling through the urinary bladder via the alfa-pump closed system in platinum-resistant ovarian cancer (PROC): First clinical experience in a cancer patient.
Authors: Fotopoulou Christina , Spiers Laura , Pickford Emily , Dina Roberto , Blagden Sarah Patricia , Habib Nagy A , Gabra Hani 
Published: March 2020

5562 Background: Malignant ascites in PROC causes significant impairment in quality of life. The Sequana Medical alfapump System (AP), a remotely controlled device connecting the patients’ peritoneal cavity to their urinary bladder, has been evaluated for the continuous drainage of ascites in liver cirrhosis, but not as yet for malignant ascites. Methods: We implanted the AP in the peritoneal cavity of a 67y old heavily pretreated PROC patient with recurrent malignant ascites requiring 3-5 liters drained 3 times/month. The AP was evaluated for its ability to drain ascites into the urinary bladder using an electronic download of recorded volume pumped, cross correlated with weekly ultrasound, symptomatic scores and QoL evaluation. Early morning urine for evaluation of urinary cytology and tumor-cell molecular analysis was collected weekly. Results: The implantation was performed under general anaesthesia in a 60 minute procedure. Before insertion the patient had 3 liters of malignant ascites; 2 liters were drained during surgery. The pump, draining 350ml ascites per day successfully drained the ascites to dryness after 3 days. The patient underwent weekly sonography and monthly cystoscopies. She did not report pollaki- or dysuria, only an increased micturition volume. Histopathological analysis of the urine revealed rich malignant cell content, used to create FFPE cell blocks weekly for molecular- pathological profiling with sequential Caris Target Now analysis and full exome sequencing. Conclusions: On initial evaluation, the AP represents a tolerable and effective means of diverting peritoneal ascites into the urinary bladder and thus preventing its recumulation in PROC. This innovative approach not only addresses an area of unmet need for the control of malignant ascites but also provides a method of collecting tumor tissue and evaluating longitudinal change in molecular tumor characterization. A EUTROC multicenter European randomized trial (AMAZE) is planned for evaluation of clinical and translational implications of the AP in PROC.
Exploratory analysis of nibrin in advanced ovarian cancer (AOC) patients treated in the phase III OVA-301 trial.
Authors: Aracil Avila Miguel , Nieto Antonio , Tanovic Adnan , Monk Bradley J. , Kaye Stanley B. , Poveda Andres , Herzog Thomas J. , Parekh Trilok V. , Badri Nadia , Galmarini Carlos 
Published: March 2020

5566 Background: Nibrin (p95/NBS1) is a protein with an essential function in DNA double-strand break repair by homologous recombination. Therefore, we have investigated its value as a possible biomarker in patients with AOC by immunohistochemistry (IHC). Methods: IHC staining was performed in 138 samples from a subset of patients that have participated in the phase III OVA-301 trial, in which the combination of trabectedin plus pegylated liposomal doxorubicin (PLD) or PLD alone were randomly administered for advanced disease after failure of platinum-based chemotherapy (Monk 2010; Monk 2012). A computerized image analysis system was used to calculate the total percentage of nibrin-positive cells. Nibrin expression was considered as a continuous variable. The analysis of overall response rate (ORR) and progression-free survival (PFS) was based on independent oncologist assessment. Overall survival (OS) was defined from randomization to death/last contact. All the comparisons had an exploratory nature; an alpha cut-off value of 0.05 (two-sided) was established as statistically significant. Results: For PFS, there was a statistically significant correlation between high levels of nibrin and short PFS (HR = 1.014, 95% CI: 1.004-1.024, p=0.0047). Similarly, for OS, there was a statistically significant correlation between high levels of nibrin and worse OS (HR = 1.009, 95% CI: 1.001-1.017, p = 0.0295). A multivariate analysis showed that high levels of nibrin were independently correlated to a worse PFS (HR = 1.012, 95% CI: 1.002-1.022, p = 0.0147) and to a worse OS (HR = 1.010, 95% CI: 1.002-1.018, p=0.0192). After stratification according to platinum-sensitivity, high nibrin showed a significant correlation with lower ORR (ORR = 1.02, 95% CI: 1.01-1.03, p=0.0009), short PFS and OS values only in the platinum-sensitive patients. Conclusions: The results point out the potential importance of nibrin expression in the clinical outcome of patients with AOC. In particular, high protein expression of nibrin seems to be associated with a worse clinical outcome. Prospective clinical trials evaluating the clinical usefulness of this marker with other standard of care treatments are warranted. Clinical trial information: NCT00113607.
Results of the MARS study on the management of antiangiogenics’ renovascular safety in ovarian cancer.
Authors: Launay-Vacher Vincent , Janus Nicolas , Selle Frédéric , Goldwasser Francois , Mir Olivier , Spano Jean-Philippe , Thery Jean Christophe , Beuzeboc Philippe , Rey Jean-Baptiste , Jouannaud Christelle , Morere Jean F. , Oudard Stephane , Gligorov Joseph , Azizi Michel , Dorent Richard , Deray Gilbert , Ray-Coquard Isabelle Laure , Scotte Florian 
Published: March 2020

5567 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1,124 pts were included. 79 pts had ovarian cancer (OC) and all received bevacizumab. Median age at inclusion was 61 years. Visceral, bone and cerebral metastasis frequencies were 74.1, 52.7 and 6.0%, respectively. HTN prevalence was 16.5%. Baseline renal assessment retrieved: Pu 36.0%, Hu 21.3%, mean aMDRD 83.0 ml/min/1.73m2 and 5 pts with aMDRD<60. The incidence of de novo Pu and HTA during f/u was 56.8 and 21.2% (Table). 88.9 % of pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 64.0% afterwards improved/normalized. No Grade 4 Pu has been reported (at inclusion or during f/u). Renal function remained stable with a mean aMDRD of 83.2 at the end of f/u. 6.0% had grade 2 SCr increase (no grade 3-4). No thrombotic micro-angiopathy (TMA) was reported. Conclusions: These results on the renovascular safety of bevacizumab in OC patients showed that 1) TMA is rare, 2) Pu develops in 56.8% of the pts, however with only 1 Grade 3/4, 3) 21.2% developed HTN, and 4) aMDRD was stable. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]