bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.
Authors: Carus Andreas , Ladekarl Morten , Nielsen Patricia Switten , Hager Henrik , Nedergaard Bettina S , Steiniche Torben , Donskov Frede 
Published: March 2020

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p <0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (<0.019), II (0.02-0.05), III (0.06-0.24), and IV (>0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.
Ovarian cancer distribution of histology, stage, and screening performance.
Authors: Eiriksson Lua R , Reade Clare J , Lennox Genevieve , Mojtahedi Golnessa , Murphy Joan , Ferguson Sarah E , Bernardini Marcus Q 
Published: March 2020

5543 Background: Survival in women with ovarian cancer is strongly influenced by stage of disease at diagnosis. As such, strategies have been investigated to identify biomarkers for early detection. This premise assumes a progression of disease from early to late stage. Varying histologic subtypes in ovarian cancer have distinct etiologies. It is likely that early detection strategies will need to be subtype specific. This study sought to evaluate histologic subtypes, stage of disease, and screening performance in a cohort of women diagnosed with ovarian cancer. Methods: This analysis was performed as an REB approved sub-study of a single institution ovarian cancer tumor banking protocol for which all patients presenting with suspected ovarian cancer, since February 2011, were eligible. This analysis included all patients with confirmed ovarian cancer. Patients were identified and tracked prospectively. Results: There were 135 patients with ovarian cancer (mean age 57 ± 12 years). 67% were post-menopausal. The distribution of histologic subtypes was 42% high-grade serous (HGS), 18% endometrioid, 12% clear cell, 6% low-grade serous (LGS), 6% sex-cord stromal, 5% germ cell, 3% mucinous, 3% mixed, 3% carcinosarcoma, and 2% other. 64 (47%) women presented with advanced disease with a median CA 125 of 260 (range 14 – 21 782), of whom 43 (68%) were found to have HGS histology. 46 (34%) patients presented with stage I disease with a median CA 125 of 41 (range 3 – 9305). Of these, the distribution of histologic subtypes included 13 (28%) endometrioid, 9 (20%) clear cell, 5 (11%) sex-cord stromal, 5 (11%) HGS, 3 (7%) mucinous and 23% other. Risk of Malignancy Index (RMI) scoring for women with stage I disease (N = 35) revealed a false negative rate of 31%, including 4 clear cell, 2 LGS, 2 endometrioid and 1 each of HGS, mucinous, and mixed (clear cell and endometrioid) histologies. Conclusions: Stage I ovarian cancer consists primarily of non-serous histologies, which are not reliably detected using CA 125 and ultrasound markers. Current approaches to screening for early stage disease may require the identification of biomarkers unique to clear cell and endometrioid histologies and novel strategies for the identification of patients at risk for HGS carcinomas.
Tasisulam-sodium in combination with liposomal doxorubicin in patients with ovarian cancer.
Authors: McMeekin D. Scott , Rosen Lee S. , Bessudo Alberto , Tai Datchen Fritz , Ilaria Robert L. , Chen Jian , Turner P. Kellie , Krueger Sandia , Gordon Michael S. 
Published: March 2020

5551 Background: Tasisulam-sodium (TASI) is a novel, highly albumin-bound small molecule that induces tumor cell apoptosis and has antiangiogenic activity. This phase 1b study was designed as a dose-finding study for TASI in combination with liposomal doxorubicin (DX) in patients (pts) with advanced solid tumors, followed by a dose-confirmation phase in platinum-resistant DX-naïve ovarian cancer (OvCa) pts. However, the study was stopped early for business reasons. Nonetheless, the dataset allowed partial characterization of the safety and antitumor activity of TASI + DX among OvCa pts who achieved an albumin-corrected exposure (AUCalb) within a hypothesized therapeutic range identified in phase II monotherapy trials. Methods: In the dose-escalation phase (3+3 schema), pts received TASI (escalating Cmax targets of 300-380 μg/mL, 2-h IV) plus DX (40 mg/m2, 1-h IV) every 28 days. Pharmacokinetic and safety analyses identified an AUCalb target of 3500 h*μg/mL for the dose-confirmation phase. We analyzed data for OvCa pts from both phases who achieved TASI AUCalbof 1200-6400 h*μg/mL in cycle 1. Results: Of the 13 OvCa pts who completed the dose-escalation phase and 6 OvCa pts who completed the dose-confirmation phase, 10 had AUCalbof 1200-6400 h*μg/mL in cycle 1. For these pts, the most common possibly drug-related Grade 3-4 adverse event was neutropenia (see table). Although no pt achieved complete response, 2 pts achieved partial response. Data from the other OvCa pts will also be presented. Conclusions: The early closure of the study did not allow complete assessment of TASI in combination with DX; however, acceptable tolerability and some antitumor activity were observed for OvCa pts with TASI AUCalbwithin the hypothesized therapeutic range. Clinical trial information: NCT01214668. [Table: see text]
Phase II study of trabectedin in pretreated patients with recurrent epithelial ovarian cancer (REOC).
Authors: Marinaccio Marco , Mele Emilia , Lorusso Vito , Fumarulo Valeria Vincenza , Sozzi Fausta , Cicinelli Ettore 
Published: March 2020

5559 Background: The prognosis of patients with REOC is extremely poor after several lines of chemotherapy. The choice and timing of therapies must be individualized to optimize survival and quality of life. This open-label, nonrandomized, phase II study was aimed at evaluating efficacy and toxicity of Trabectedin as a single-agent therapy in patients with preteated Recurrent Epithelial Ovarian Cancer (REOC). Methods: Sixteen patients (median age 51 yrs, range 44 – 71) with REOC who progressed after 2 (18.7%), 3 (56.3%) or 4 (25.0%) previous lines of chemotherapy were treated with Trabectedin at the dose of 1.1 mg/m2 via a 3-hour i.v. infusion with dexamethasone pretreatment every 3 weeks until disease progression, unacceptable toxicity or when a stability of disease was reached. Clinical objective response was the primary efficacy endpoint; the secondary one was safety. Response to treatment was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), and toxicities were graded according to NCI Common Toxicity Criteria, version 2.0. Results: The median number of treatment cycles per patients was 5 (range, 2-9 cycles). A total of 81 cycles were administered. A dose reduction was never required. Main toxicities included anemia (20.9%), leucopenia (15.0%), thrombocytopenia (4.5%) and asthenia (22.2%). No deaths were attributable to therapy. No one showed complete response, while 9/16 partial response (56.2%) and 4/16 stable disease (25.0%) were observed. 3/19 pts (18.8%) progressed on therapy. The median progression-free interval was 18 weeks in patients with partial response; stable disease was maintained for a median time of 12 weeks. Conclusions: Trabectedin 1.1mg/m2 given as a 3-hour i.v. infusion every 3 weeks was well tolerated and has confirmed a very interesting antitumor activity in this heavily pretreated population and it seems also to be a very tolerable regimen. The co-treatment with dexamethasone improves the safety of Trabectedin by reducing drug-induced myelosuppression and hepatotoxicity. Trabectedin has a manageable toxicity profile, and can be safely administered thanks to its secure action profile also in patients with no other viable therapeutic options.
An open label, randomized, parallel, phase II trial to evaluate the efficacy and safety of cremophor-free, polymeric micelle formulation of paclitaxel compared to paclitaxel in subjects with ovarian cancer.
Authors: Kim Yong-Man , Lee Shin-Wha , Cho Chi Heum , Hur Soo-Young , Kim Byoung-Gie , Kim Jae Hoon , Kim Seung Cheol , Kim Seok-Mo , Kim Young-Tae , Ryu Hee Sug , Kang Soon-Beom 
Published: March 2020

5568 Background: Cremorphor EL, used to enhance drug solubility, may add to paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. This multi-institutional phase II trial is to evaluate the efficacy and safety of Cremophor-Free, Polymeric Micelle Formulation of Paclitaxel (Genexol-PM) compared to Paclitaxel (Genexol) as a combined chemotherapy with carboplatin in patients with advanced epithelial ovarian cancer. Methods: In this phase II, randomized, parallel study, patients with FIGO stage IC-IV epithelial ovarian cancer after debulking surgery received intravenously Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 combined with carboplatin iv (AUC 5) on day 1 of every 3-week cycle for a maximum of six cycles. The primary endpoint was composite response by GCIG CA-125 Response and Response Evaluation Criteria In Solid Tumors (RECIST). Secondary and exploratory endpoints included overall survival, progression-free survival, time to tumor progression, and safety and tolerability. Results: A total of 102 patients were randomized to Genexol-PM plus carboplatin (n = 51) or Genexol plus carboplatin (n = 51). Composite response rate in patients with or without measurable disease was 88.0% in the Genexol-PM plus carboplatin group and 77.1% in the Genexol plus carboplatin group. Noninferiority of Genexol-PM plus carboplatin compared with Genexol plus carboplatin was confirmed for composite response rate by CA-125/RECIST criteria. There were no differences in progression-free survival and overall tumor progression between the groups. Although there was a higher rate of grade 3 neutropenia in the Genexol-PM plus carboplatin group, the overall rate of hemodynamic adverse events was comparable between the 2 groups. There was no difference in peripheral neuropathy and hypersensitivity. No unexpected safety concerns were identified in this study. Conclusions: High-dose of Genexol-PM in combination with carboplatin was well tolerated, and its response rate was noninferior to that of Genexol plus carboplatin in patients with advanced epithelial ovarian cancer. Clinical trial information: NCT01276548.
Chemotherapy-induced myelosuppression in ovarian cancer patients with germline BRCA1/2 mutations: A case control study.
Authors: Christie Alan , Che Bakri Amalina , Roxburgh Patricia , Khan Muhammad Imtiaz , Iqbal Yousuf , Rye Tzyvia , Mitchell Paul , Rye Ronald , Nussey Fiona , Mackean Melanie J. , Reed Nicholas , Glasspool Rosalind Margaret , Ferguson Michelle , Gourley Charlie 
Published: March 2020

5571 Background: Ovarian cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2) mutations frequently respond to multiple lines of chemotherapy. Having noticed significant myelosuppression during chemotherapy in gBRCA1/2 patients we wished to determine whether this was a chance finding or related to a heterozygous gene dosage effect in the bone marrow. Methods: gBRCA1/2 ovarian cancer patients from Edinburgh, Glasgow and Dundee were identified and matched for chemotherapy regimen, dose and age to controls from the Edinburgh Ovarian Cancer Database. Case notes and transfusion service records were analysed for chemotherapy details, haematology results, G-CSF use, red cell and platelet transfusions during first line chemotherapy. Results: Of 91 gBRCA1/2 patients, 35 patients were excluded who had previously received cytotoxic chemotherapy (mostly for breast cancer) or unusual chemotherapy regimens unable to be matched to controls. 56 were matched to controls. Baseline haematological indices were similar. There was a significant difference in the fall in haemoglobin levels from baseline to cycle 4 in gBRCA1/2 patients compared to controls (12.23% v 5.14%, p = 0.0005) and gBRCA1/2 patients had longer delays during their chemotherapy (mean 7.73 v 4.51 days, p = 0.0375) and more dose reductions for haemotoxicity (14 v 4 p = 0.0011). gBRCA1/2 were more likely to have a red cell transfusion (19 v 11, p = 0.099), and received more red cells (69 v 31 units, p = 0.0318). G-CSF was required in 3 BRCA patients versus 0 controls. Differences in platelet and white cell counts at cycle 4 were not significant. Conclusions: Patients with ovarian cancer and germline BRCA1/2 mutations were more likely to have significant falls in haemoglobin levels and require red cell transfusions and to experience delays during chemotherapy. This susceptibility to anaemia may be a hemizygous BRCA1/2 gene dosage effect manifest in the bone marrow and may have implications for the optimisation of cytotoxic and PARP inhibitor therapy in this patient group.
A panel of biomarkers to improve specificity in presurgical assessment of adnexal masses for risk of ovarian malignancy.
Authors: Zhang Zhen , Li Danni , Sokoll Lori J. , Sun Xiaer , Bristow Robert , Chan Daniel W 
Published: March 2020

5573 Background: OVA1 is a panel of biomarkers cleared by FDA currently in clinical use for pre-surgical assessment of adnexal masses for risk of ovarian malignancy. To further improve the specificity of OVA1, we evaluated biomarkers using a designed set of clinical samples enriched with OVA1 false positive benign patients and selected insulin-like growth factor binding protein 2 (IGFBP2), interleukin 6 (IL6), and follicle-stimulating hormone (FSH) to be further evaluated along with the original five biomarkers of OVA1 on a prospectively collected clinical sample set. The inclusion of FSH was to eliminate the need for menopause-specific cutoffs. Methods: Consecutive patients with a documented pelvic mass planned for surgical intervention were prospectively enrolled at 27 sites. Exclusion criteria included a diagnosis of malignancy in the previous 5 years or initial enrollment by a gynecologic oncologist. At the time of analysis, 384 subjects had all biomarker values. Among them 69 were ovarian cancer cases (13 LMPs, 27 stages 1/2, 19 serous, 11 endometrioid , 5 mucinous, and 4 clear cell). Biomarkers were tested by ELISA and reported as continuous values. Using a subset of the samples, the biomarkers were first selected for inclusion in a final panel based on contributions in multivariate models estimated by bootstrap. The selected biomarkers were further assessed for ability to improve specificity of risk stratification at a fixed sensitivity over that of OVA1 using the full data set. This was done by cross-validation of multivariate models with 50/50 split between training and testing. Results: The final panel of biomarkers consisted of CA125II, prealbumin, IGFBP2, IL6, and FSH. At a fixed sensitivity of 90%, the mean and median specificity of models using the new panel in testing were 78.2% (95% CI: 76.7 – 79.8%), and 80.6%, respectively. The mean and median absolute improvements over that of OVA1 were 18.6% (95% CI: 16.4% – 20.9%) and 20.3%, respectively. Conclusions: The new panel demonstrated the potential to significantly improve specificity over that of the first-generation OVA1 algorithm, while maintaining a high sensitivity in pre-surgical assessment of adnexal masses for risk of malignancy.
Is uterine serous carcinoma a part of hereditary breast cancer syndrome?
Authors: Rafii Saeed , Dawson Philip , Williams Sarah , Pascoe Jennifer S. , Nevin James E. , Sundar Sudha 
Published: March 2020

5587 Background: Whilst the association between breast cancer and uterine serous carcinoma (USC) is attributed to tamoxifen treatment, few studies have reported that this increased risk is independent of tamoxifen. Methods: To further investigate the relationship between breast cancer and USC, we retrospectively studied 216 patients from 5 hospital trusts in Birmingham, UK who were diagnosed with USC between 1993 and 2012. We collected personal history of cancer in these cases before or after USC diagnosis. In addition FIGO staging, clinical and survival data were collected from our local cancer registry and patients’ clinical records. Results: In this case series, 56 patients (25.9%) had personal history of at least one cancer before and 18 patients (8.3%) had history of at least one cancer after the diagnosis of USC. Within the group of patients with the history of cancer before the USC, 38 patients (68%, 17.5% of all cases) had personal history of breast cancer prior to the development of USC, higher than the UK expected age standardised relative incidence of breast cancer (350 in 100,000, CRUK 2006-2008). Although 27/38 cases (71%) had endocrine treatment for their primary breast cancer, 11/38 patients (29%) did not have any tamoxifen treatment due to hormone receptor negative breast cancer. Additionally the median age of breast cancer diagnosis for the hormone receptor negative group was significantly lower than those patients who had hormonal treatment for their breast cancer (56 vs. 64 years, p :0.036) compatible with the younger age at diagnosis expected of the familial (BRCA mutated) or triple negative breast cancer. Of 18 patients with a second cancer after diagnosis of USC, 6 patients (33%) were diagnosed with breast/ovarian cancer. This group also had no treatment with tamoxifen. Conclusions: Lack of exposure to tamoxifen and younger age at diagnosis in this subgroup suggest that other factors such as a common underlying genetic predisposition may be responsible for the development of both malignancies. We propose that at least a subgroup of USC may be a part of hereditary breast cancer syndrome. This may have implications in prevention (prophylactic hysterectomy) or trials of targeted treatments (PARP inhibitors) for a subgroup of USC patients.
Tissue sampling frequency and breast pathology diagnoses following mammography: Time trends and age group analysis from the Breast Cancer Surveillance Consortium (BCSC).
Authors: Allison Kimberly H. , Abraham Linn A , Weaver Donald L. , Tosteson Anna NA , Onega Tracy , Geller Berta M , Kerlikowske Karla , Carney Patricia A , Ichikawa Laura E , Buist Diana SM , Elmore Joann G 
Published: March 2020

559 Background: Pathology diagnoses in a well-characterized population of women can be used to identify tissue sampling and diagnosis trends following mammography. Methods: Screening and diagnostic mammography, patient characteristics, and pathology reports from the BCSC performed from 1996-2008 were identified. Diagnosis was based on the most severe pathology interpretation in the same breast within 60 days of a post-mammogram tissue sample. Age, mammogram year and type, breast density, and family history of breast cancer were evaluated for associations with tissue sampling and most severe pathology diagnosis. Results: 4,022,506 mammograms (88.5% screening; 11.5% diagnostic) were performed in 1,288,886 women; 76,567 (1.9%) were followed by tissue sampling (1.2% screening; 7.1% diagnostic). Tissue sampling frequency following diagnostic mammography increased over time in women over 50 but remained stable following screening mammography. The frequency of invasive cancer increased with age and was more common following a diagnostic (29.3%) vs screening (19.8%) mammogram; the frequency of high risk lesions (ADH; lobular neoplasia) was highest in women aged 50-59. For tissue sampling following screening mammograms, the frequency of DCIS increased over time while benign diagnoses decreased. No significant time trends were noted for diagnoses associated with diagnostic mammograms. Women aged 40-59 with dense breasts and a tissue sampling following screening mammogram had a significantly higher frequency of DCIS (40-49: 4.8% vs 3.2%, P< 0.001; 50-59: 7.0% vs 5.7%, P=0.007). Women aged 40-59 with > 1first degree relative with breast cancer vs none that had a tissue sampling following screening mammogram had a significantly higher frequency of invasive cancer (40-49: 11.4% vs 9.4%, p=0.008; 50-59: 19.8% vs 18.2%, p =0.086) and DCIS (40-49: 6.2% vs 4.0%, p< 0.001; 50-59: 8.2% vs 6.2%, p< 0.001). Conclusions: There was an increase in DCIS and a decrease in benign diagnoses in tissues samples after screening mammography over time. No trends were seen following diagnostic mammography. DCIS was also more frequent in women with dense breasts.