bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and association with time to treatment change in patients with metastatic renal cell carcinoma
Authors: Liu Z. , Burke J. , Zheng J. , Johnson J. 
Published: August 2020

e16160 Background: Metastatic renal cell carcinoma (MRCC) is associated with high mortality rates. The objectives of this study are to examine survival rates among patients using targeted therapies (Sunitinib, Sorafenib) for MRCC and the association of time to treatment change with survival. Methods: Administrative claims data from a large, US managed care plan were used to identify commercially insured and Medicare patients with newly diagnosed MRCC from 01/01/03–12/31/07 and continuous enrollment for 12 months prior to and at least 90 days after MRCC diagnosis. Survival from earliest evidence of targeted therapy (TT) was assessed through 9/16/2008. Treatment change was defined as stopping TT, switching TT or the addition of other treatments for MRCC. Results: 253 patients were identified with newly diagnosed MRCC (average age: 60.5 years; 71.5% male) who also received TT. Mean (median) survival time from initiation of therapy was 533 (507) days. A majority of those on TT (n = 205, 81.0%) experienced treatment change within 6 months after initiating the therapy; two-thirds within 30 days of therapy initiation. Unadjusted survival rates increased significantly with longer time to change in treatment (p=0.0075), with a mean survival time of 437 days for those with treatment change within 30 days and 724 days among those with treatment change 5–6 months post therapy initiation. Conclusions: Early treatment changes are associated with shorter survival times. High rates of early treatment changes indicate inadequacies in currently available targeted therapies for MRCC patients. No significant financial relationships to disclose.
Predictive value of serum CA125 levels in women with persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) treated with bevacizumab (Bev) on a Gynecologic Oncology Group (GOG) phase II trial
Authors: Randall-Whitis L. , Burger R. A. , Sill M. , Monk B. J. , Buening CCRC B. , Sorosky J. I. 
Published: August 2020

e16505 Background: The clinical utility of serum CA125 in patients (pts) with EOC/PPC treated with biologic agents is unknown. The primary objective of this study was to determine the proportion of pts treated with bevacizumab on a phase II clinical trial with stable disease by RECIST who demonstrated disease progression (pgrn) as assessed by modified GCIG CA125 criteria. Methods: Sixty-two pts with measurable recurrent or persistent EOC/PPC were treated with bevacizumab 15 mg/kg Q 21 days on a phase II clinical trial. Primary endpoints of the clinical trial were progression-free (PF) survival at 6 months and response assessed by RECIST criteria. Pts were removed from therapy/evaluation for disease prgn by RECIST, toxicity, or by subject request. Serum CA125 was collected at entry and prior to each cycle but levels were only used to define a complete response which required CA125 normalization (≤35). Modified GCIG criteria were retrospectively applied to these CA125 values to determine time to progression from date of entry to either the first time CA125>70 for pts whose CA125 normalized on treatment or was greater than 2X the nadir value for pts whose CA125 did not normalize. Censored cases provided time until the date of last CA125 measurement. Results: The median PFS by RECIST was 4.7 mos. Of those patients who had prgn by CA125, the median residual time to prgn by RECIST was 1.4 mos. In all, twenty-five (40.3%) pts survived PF for 6 mos. by RECIST and 16 (25.8%) by CA125. Ten pts who survived PF for at least 6 mos. by RECIST indicated treatment failure before 6 mos. by CA125, or 40% of the 25 positive outcomes. Eight pts continued to receive treatment for at least 4 mos. after prgn by CA125, with one continuing therapy for more than 3 years. Conclusions: Serum CA125 levels were a useful marker of progression in some pts treated on this trial; however, some pts received clinical benefit from continued therapy in spite of indications of disease prgn by CA125. Consideration should be given before discontinuing bevacizumab therapy based on CA125 progression alone. No significant financial relationships to disclose.
Expression and signaling of Toll-like receptor 4 (TLR4) and MyD88 in ovarian carcinoma cells
Authors: Szajnik M. E. , Szczepanski M. J. , Czystowska M. , Elishaev E. , Mandapathil M. , Nowak-Markwitz E. , Spaczynski M. , Whiteside T. L. 
Published: August 2020

e16508 Background: TLR4, expressed by the cells of the immune system play a role in the protection of the host against pathogens. TLRs are also expressed on human cancer cells, but their role in tumor growth is unknown. The aim of this study was to correlate the presence of TLR4 and MyD88 expression with clinicopathologic outcome in patients with ovarian cancer and to analyze the consequences of signaling via the TLR4/MyD88 pathway in ovarian cancer cell lines. Methods: Tumor specimens from 41 patients with ovarian carcinoma were evaluated for TLR4 and MyD88 by immunohistochemistry and correlated with clinical and pathologic disease features. TLR4/MyD88 expression in OVCAR3, SKOV3, and A2780 was determined using RT-PCR, WB, and immunohistochemistry. NF-kB translocation to nucleus was measured by confocal microscopy. Culture supernatants were tested for levels of cytokines in Luminex-based assays. Proliferation of cancer cells was measured in the CFSE assays. Their sensitivity to paclitaxel (PLX) was measured by Annexin V binding. Western Blot analysis was used to measure activation of the PI3K/Akt, IRAK 1, IRAK 4, and TRIF. Results: In ovarian cancer patients TLR4 and MyD88 expression by the tumor was observed in 100% and 83% of tissues, respectively. The expression of MyD88 was associated with shorter progression-free survival (42 vs 31 months, p < 0.05). Ex vivo studies showed that TLR4 was expressed on OVCAR3, SKOV3, and A2780 cell lines, while A2780 did not expressed MyD88. In MyD88+ tumor cells, LPS increased proliferation (PI 17 vs 8, p < 0.05), activated NF-kB pathway and promoted cytokine production (IL-8, IL-6, RANTES, VEGF and MCP-1). LPS and PLX binding to TLR4 on MyD88+ cells induced activation of PI3K/Akt, IRAK4, and IRAK1, but decreased expression of pro-apoptotic TRIF. In contrast, in MyD88(-) cells LPS did not induce proliferation and neither LPS nor PLX induced secretion of pro-inflammatory cytokines. Further, no changes were noted in IRAK1 expression, but strong signal was observed for TRIF. TLR4+/MyD88+ tumor cells showed grater resistance to PLX. Conclusions: Our ex vivo studies elucidate the molecular mechanisms involved in TLR4/MyD88 signaling. Ligation via TLR4 leads to tumor growth, release of proinflammatory cytokines and induction of resistance to PLX-induced apoptosis. No significant financial relationships to disclose.
Survival with surgical versus medical treatment of patients with bowel obstruction secondary to ovarian cancer recurrence: A 15-year experience
Authors: Al-Niaimi A. , Manuelli B. , Safdar N. , Chappell R. , Seo S. , Kushner D. , Connor J. , Hartenbach E. 
Published: August 2020

e16515 Background: To compare the impact of surgical versus medical management on the survival of patients presenting with small bowel obstruction (SBO) secondary to recurrent ovarian cancer. Methods: The Institutional Review Board approved a retrospective chart review of all patients with SBO due to recurrent ovarian cancer at the University of Wisconsin Hospital between January 1, 1992, and December 31, 2007. The data abstracted from patient charts included demographics, primary cancer characteristics, detailed clinical information at the time of SBO, management strategy, and outcome. Univariate analysis was performed with Cox proportional hazard model and Kaplan-Meier curves were generated for survival. Results: 71 patients met our search criteria, 6 were excluded because of a paucity of medical information. Of the 65 patients in our study, the median age was 53 years. 86% of the patients had stage III/IV ovarian cancer, while 14% had stage I/II. The median time from tumor recurrence to bowel obstruction was 17 months. 41% of patients presented with high grade bowel obstruction while 69% were low grade. 36 (55%) of patients underwent surgery for management of bowel obstruction and the remaining 29 (45%) were managed conservatively with various medical approaches. Two-year survival for the surgically managed patients was 38% compared to 18% for those who received medical treatment (p = 0.07). There was no difference in survival for patients based on histology (p = 0.38), grade (p = 0.077), grade of SBO (p = 0.56). Patients with stage I/II had a median survival of 50 months versus stage III/IV at 3.5 months (p = 0.01). Median survival for patients without ascites at time of SBO was 9.5 months while those with ascites was 3 months (p = 0.0004). Patients without abdominal or pelvic mass on CT had a median survival of 60 months; patients with any mass noted had a median survival of 3.6 months; patients with liver and lung metastases was 3 months (p = 0.001). Conclusions: In patients with bowel obstruction due to ovarian cancer recurrence; early stage at diagnosis, the absence of ascites, and lack of abdominal/pelvic mass or distant metastases significantly lengthens survival. There is a trend towards the superiority of surgical management in these patients. No significant financial relationships to disclose.
Quality of care in advanced ovarian cancer: How important is provider specialty?
Authors: Mercado C. , Zingmond D. , Karlan B. Y. , Sekaris E. , Gross J. , Maggard-Gibbons M. , Tomlinson J. S. , Ko C. Y. 
Published: August 2020

e16519 Background: Ovarian cancer is one of the most aggressive and deadly cancers in women. While the mainstay of therapy is surgery, ovarian cancer surgical procedures are performed by surgeons with different specialty training, including gynecology, gynecologic oncology, general surgery, and others. We examine the degree to which surgeon specialty impacts survival and other quality of life-related outcomes in advanced ovarian cancer patients. Methods: Analyses of Stage 3c/4 ovarian cancer patients were performed from 4 states (California, Washington, New York, Florida). Four databases were linked for each state: cancer registry, inpatient-hospital discharge, AMA masterfile, and 2000 U.S. Census SF4 File. Multivariate modeling was performed to identify predictors of survival as well as proxy quality of life-related outcomes, as measured by creation of a fecal ostomy. Hospital case volume was defined as low volume (LV) [0–4 cases], middle volume (MV) [5–9], high volume (HV) [10–19], and very high volume (VHV) [20+]. Results: 60,405 ovarian cancer patients were identified; 53% were Stage 3c/4. Mean age was 64 years. Patients had lower hazard of death when treated in higher volume hospitals as compared to LV [HV (Hazard Ratio) HR = 0.89, p < 0.0001; VHV HR = 0.79, p < 0.001]. Patients treated by gynecologists/gynecologic-oncologists had lower hazard of death (HR = 0.61, p < 0.0001) as compared to other surgeons (non-gynecologist), controlling for hospital type, case volume, comorbidity, and demographics. Also, patients treated by a trained gynecologist had the lowest chance of having an ostomy performed as compared to those of other specialties (HR = 0.22, p < 0.0001). Factors associated with receiving treatment from a non-gynecologist included low volume, rural patient residence, poverty, and high comorbidity. Conclusions: Stage 3c/4 ovarian cancer patients have better survival when treated by gynecology-trained surgeons. Our data suggest that gynecology-trained specialists optimize quality of life-related outcomes, specifically minimizing the creation of a fecal ostomy. Surgeon specialty was more important than procedure volume for these outcomes. Referral to gynecology-trained surgeons would improve survival and quality of life outcomes in advanced ovarian cancer patients. No significant financial relationships to disclose.
Six versus nine cycles of paclitaxel-carboplatin as first-line chemotherapy in patients with newly diagnosed epithelial advanced ovarian cancer
Authors: Nayl B. , Durando X. , Pomel C. , Dubray P. , Mouret-Reynier M. , Le Bouedec G. , Gimbergues P. , Chollet P. , Dauplat J. , Cure H. 
Published: August 2020

e16535 Background: A multimodality approach with cytoreductive surgery and six courses of paclitaxel-platinum-based chemotherapy is actually the mainstay of treatment of Advanced Ovarian Cancer (AOC). This study was performed to determine retrospectively the efficacy of three additional cycles of paclitaxel-carboplatin (PC) in patients with AOC who had previously demonstrated chemosensitivity to six courses of this regimen. Methods: From January 2000 to August 2008, 125 epithelial AOC (FIGO stages IIIC and IV) were diagnosed in a single institution. After a cytoreductive surgery, 51 patients received six cycles of PC (PC 6 group), 57 received 9 (PC 9 group), and 17 experienced progressive disease during treatment. The chemotherapeutic regimen consisted of intravenous paclitaxel 175 mg/m2 for a 3-hour infusion period and intravenous carboplatin AUC 5 every 3 weeks. Results: Median age was 62 years in PC6 group and 59.7 years in PC9. According to the FIGO criteria, 72.6% patients were in stage IIIC in group PC6 and 75.4% in group PC9. Except the patients who experienced refractory disease, complete clinical response at the end of chemotherapy was assessed in 71.4% patients in group PC6 and 71.9% in PC9 (p = 0.13). The median time to progression (TTP) was 26.2 months in PC6 and 29 months in PC9 (p = 0.5). The median overall survival (OS) was 106 months and 97 months respectively (p = 0.16). Conclusions: This retrospective study suggests that three cycles of consolidation chemotherapy with paclitaxel and carboplatin might not prolong duration of TTP or OS in AOC patients. No significant financial relationships to disclose.
iGenomicViewer, a Gynecologic Oncology Group software library for the creation of highly customizable, portable, interactive, and linked visualizations of high throughput genomic data
Authors: Gaile D. P. , Shepherd L. , Liu S. , Darcy K. , Brady M. , Morrison C. 
Published: August 2020

e16544 Background: An R software library was created with the goal of creating customizable, platform independent, and portable visualization tools for the annotation, dissemination and interrogation of high dimensioned genomic data. Methods: A set of R functions were created to extend the functionality of the sendplot R library. The functions were applied to BAC aCGH data generated for several GOG studies. Results: The iGenomicViewer function calls created and populated a directory structure which was then ported to a password protected server for interrogation by research team members. The linked html and image output allows users to examine genome wide plots of aberration frequencies and p-values and then drill down to visualizations of regions of interest. Users can interrogate a panel of plots which includes: 1) a heat map of the aCGH data for with tool-tip display of sample and assay specific data (e.g., assay values, sample IDs, and hyperlinks to UCSC browser and sample specific images); 2) a set of interactive annotation tracks which display location of cancer, disease and DNA repair genes; and 3) a plot which displays -log10 p-values and/or aberration frequencies for the BAC assays depicted in the heatmap. For the smallest regions of interest, the panel of plots contains a tiled heatmap which depicts the overlap and gaps in BAC coverage and their alignment with the gene locations represented in the adjacent annotation track. Conclusions: The iGenomicViewer library provides open source software for creation of customizable visualization tools for collaborative research projects involving high dimensioned genomic data. No significant financial relationships to disclose.
Clinical outcome of resection of liver metastasis in patients with ovarian cancer
Authors: Neumann U. P. , Fotopoulou C. , Neuhaus P. , Sehouli J. 
Published: August 2020

e16545 Background: Hepatic resection has become the standard treatment for resectable colorectal liver metastases. However, in patients with ovarian cancer resectable liver metastases are rare and the issue is discussed controversially due to the lack of relevant published data. The aim of this retrospective study was to evaluate the efficacy of hepatic resections in patients with ovarian cancer. Methods: Between 1991 and 2006 a total of 73 women with liver metastases underwent surgery for ovarian cancer. The median age of the patients was 59 years. 18 patients had primary and 55 suffered from recurrent disease. The median follow-up was 7 months (1–145 months). In 40 patients a liver resection was performed. In the remaining 33 patients the disease was unresectable. Additional procedures were: hysterectomy 15.1%, bilateral salpingo-oophorectomy 24.7%, omentectomy 32.9%, colon resection 50.7%, small bowel resection 32.9%, gastric resection 5.5%, and pancreatic resection 9.6%. Results: Residual tumor after surgery was by far the strongest predictor for outcome. Median survival in patients with no residual tumor was 65 months, < 0.5 cm 29 months, 1cm 6 months. This data clearly show that macroscopically complete surgical cytoreductive therapy improves long-term survival in patients with ovarian cancer and liver metastases. Conclusions: We still need to identify factors associated to complete debulking to minimize the number of ineffective operations. Therefore, liver resection should be always discussed if complete resection is achievable and should be part of the multimodal strategy in advanced ovarian cancer. No significant financial relationships to disclose.
Prognosis and comorbidities in stage III and IV endometrial cancer
Authors: Wright K. , Munro E. , del Carmen M. , Goodman A. K. 
Published: August 2020

e16553 Background: While endometrial cancer may be associated with many comorbid conditions, none have been characterized as changing overall prognosis. The aim of this study was to identify medical conditions or laboratory values, that may serve as prognostic factors in stage III and IV endometrial cancer. Methods: A retrospective chart review identified 112 women with stage III or IV endometrial cancer between years 1993–1998. Information about medical comorbidities and presenting lab values were collected using electronic medical records. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival method and the log rank test. Results: The average age was 64.9 yrs. 79 women (70.5%) had stage III disease and 33 women (29.5%) had stage IV disease. For those with a baseline creatinine <1.2 (n = 91), the PFS and OS were not significantly different from those with a baseline creatinine ≥1.2 (n = 17; p = 0.554 and p = 0.487, respectively). There was a non-significant trend toward worse PFS for the 41 patients with hypertension (HTN) compared to the 62 without (48.0 and 61.2 months, p = 0.191). The overall survival was significantly worse for those with HTN (38.7 months vs. 56.0 months p = 0.046). For those with known coronary artery disease, no significant difference in PFS or OS was found (p = 0.792 and p = 0.312 respectively). Those with diabetes (n = 15) did not have a significantly different PFS compared to those who did not (n = 88; p = 0.728). The OS was worse at 20.1 months for those with diabetes compared to 54.3 months for those without (p = 0.001). Baseline albumin had a significant effect on both PFS and OS. Those with an albumin <3.5 (n = 54) had a PFS of 46.2 months compared to 94.0 months for those with an albumin ≥3.5 (n = 23; p = 0.007), and the OS for those with low albumin was 44.8 months compared to 83.4 months for those with the higher albumin (p = 0.005). Conclusions: These results suggest that past medical history and some baseline laboratory values may be important in considering prognosis. In particular, patients with a history of HTN or diabetes have a worse overall survival. Those with a baseline albumin of <3.5 have a worse PFS and OS. No significant financial relationships to disclose.
Down-regulation of MDR1 by epigenetic alteration in human epithelial ovarian cancer cells
Authors: Kawakami Y. , Miyamoto K. , Takehara K. , Kumagai M. , Samura O. , Nakamura H. , Mizunoe T. , Yoshida H. , Taniyama K. , Saji F. 
Published: August 2020

e16556 Background: Ovarian cancer is one of the most lethal malignancies in women. Despite recent studies of many oncogenes and tumor-suppressor genes concerning about its progression, the details of ovarian cancer biology still remains to be unclear. P-glycoprotein (P-gp) encoded by the MDR1 gene is a membrane protein that can export many kinds of antineoplastic agents from cells, and overexpression of P-gp has been reported to be implicated in treatment failure in cancer. DNA methylation, a major epigenetic process, can affect every step in carcinogenesis as well as genetic alterations. The contribution of such epigenetic alteration to the expression of MDR1 remains largely unexplored in human ovarian cancer. Methods: In this study, we evaluated the DNA methylation status of the MDR1 gene by methylation-specific PCR. Then, the expression of MDR-1 mRNA and protein in primary epithelial ovarian cancer specimens were evaluated by real-time RT-PCR and immunohistochemistry using anti-mouse P-gp F4 monoclonal antibody, respectively. The correlation between these results and clinicopathological features was examined. Results: MDR1 was hypermethylated in 12 of 12 (100%) ovarian cancer cell lines, and 5 of 13 (38%) primary ovarian cancers by methylation-specific PCR analysis. MDR1 mRNA expression was subsequently found to be lost in ovarian cancer cell lines with methylation by both real-time RT-PCR and immunohistochemistry. Thus, MDR1expression was associated with the DNA methylation status of the MDR1 gene. Conclusions: In conclusion, MDR1 was frequently hypermethylated in human ovarian cancers. Our results suggest that epigenetic regulation might play a role in the expression of MDR1 and clinical treatment outcomes in human ovarian cancer. No significant financial relationships to disclose.