bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.
Authors: Zhiang Jianjun , Omenge Elkanah , Maina Titus , Muthoka Kapten , Kiptoo Stephen , Groopman John , Tong Yan , Ermel Aaron , Loehrer Patrick J. , Brown Darron 
Published: May 2019

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.
A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer.
Authors: Vergote Ignace , Heitz Florian , Buderath Paul , Powell Matthew A. , Sehouli Jalid , Lee Christine M. , Hamilton Anne L. , Fiorica James , Moore Kathleen N. , Teneriello Michael , Golden Lisa , Zhang Wei , Pitou Celine , Farrington Daphne L. , Bell-McGuinn Katherine M , Wenham Robert Michael 
Published: May 2019

5537 Background: p38 mitogen-activated protein kinase (MAPK) regulates cytokine production in the tumor microenvironment and enables therapeutic resistance of cancer cells. Ralimetinib (R) is a selective small-molecule inhibitor of p38α and p38β MAPKs. Methods: Main inclusion criteria: ≥18 y; recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal, cancer after first-line treatment. Phase (Ph)1b was to determine the recommended Ph2 dose (RP2D) of R administered 12-hourly (Q12H) on Days 1-10 (21-day cycle [Q21D]) in combination with gemcitabine (G: 1000 mg/m2 on Days 3 and 10) and carboplatin (C: AUC 4 on Day 3) for 6 cycles. In Ph2, patients (pts) were randomized double-blind, 1:1 to RP2D R+GC or placebo (P)+GC, for 6 cycles, followed by R 300 mg Q12H or P on Days 1-14, Q28D until disease progression. The stratified log-rank test compared progression-free survival (PFS; primary endpoint) between treatment groups in Ph2, at a 1-sided α level of 0.2. ClinicalTrials.gov, NCT01663857. Results: 118 pts received ≥1 dose of R or P (safety population); 8 in Ph1b and 110 in Ph2 (R+GC N = 58; P+GC N = 52). The RP2D for R in combination with GC was 200 mg Q12H. The study met its primary objective (median PFS: R+GC 10.3 mo vs P+GC 7.9 mo; HR = 0.773, 2-sided p = 0.246). The secondary objectives of median overall survival (R+GC 29.2 mo vs P+GC 25.1 mo; HR = 0.827, p = 0.469) or overall response rate (R+GC 46.6% vs P+GC 46.2%; p = 0.967) were not statistically significant, and 32.4% vs 25.0% of pts had normalized CA125 at the end of cycle 6. Most pts (safety population) experienced ≥1 Grade 3/4 treatment-emergent adverse event (TEAE: R+GC 63/66 [95.5%]; P+GC 48/52 [92.3%]). Decreased neutrophil count (60.6% vs 76.9%), platelet count (43.9% vs 38.5%), and white blood cell count, (30.3% vs 26.9%), anemia (22.7% vs 25.0%), and increased alanine aminotransferase (ALT) (19.7% vs 3.8%) were the Grade 3/4 TEAEs in ≥10% of pts in the R+GC and P+GC arms, respectively. Conclusions: Addition of ralimetinib to GC resulted in modest improvements in PFS. Grade 3/4 elevated ALT was more common in the ralimetinib arm. Clinical trial information: NCT01663857.
Maintenance olaparib after platinum-based chemotherapy in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Efficacy by surgical and tumor status in the Phase III SOLO1 trial.
Authors: Mathews Cara Amanda , Moore Kathleen N. , Colombo Nicoletta , Scambia Giovanni , Kim Byoung-Gie , Oaknin Ana , Friedlander Michael , Lisyanskaya Alla Sergeevna , Floquet Anne , Leary Alexandra , Sonke Gabe S. , Gourley Charlie , Banerjee Susana N. , Oza Amit M. , González-Martín Antonio , Aghajanian Carol , Bradley William Hampton , Lowe Elizabeth S. , Bloomfield Ralph , Disilvestro Paul 
Published: May 2019

5541 Background: In SOLO1 (NCT01844986), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. N Engl J Med 2018) in pts with newly diagnosed advanced OC and a BRCAm. This analysis evaluates olaparib efficacy by timing of surgery, presence of residual tumor following surgery and response status after completion of chemotherapy in SOLO1. Methods: Pts underwent cytoreductive surgery and were in clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy. Pts were stratified by response and received olaparib tablets 300 mg twice daily or placebo. Investigator-assessed PFS and objective response were assessed using modified RECIST v1.1. Results: 260 pts were randomized to olaparib and 131 to placebo; one pt did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of pts underwent upfront and interval surgery, 21% and 76% had residual and no residual macroscopic disease after surgery, and 74% and 26% entered the study in clinical CR and PR (based on electronic case report form [eCRF] data). PFS was significantly improved regardless of the timing of surgery, residual disease status after surgery or response after platinum-based chemotherapy (Table). In pts with baseline radiologic evidence of disease (n=80; eCRF), the objective response rate was 43% for olaparib (CR, 28%) and 23% for placebo (CR, 12%). Conclusions: Maintenance olaparib improved outcomes compared with placebo in pts with newly diagnosed advanced OC and a BRCAm, regardless of surgical or tumor status. Clinical trial information: NCT01844986. [Table: see text]
Modeled CA-125 kinetics during neoadjuvant chemotherapy for predicting the likelihood of optimal interval debulking surgery in ovarian cancer patients: Data from CHIVA trial (a GINECO study).
Authors: Robelin Patrick , Tod Michel , Colomban Olivier , Louvet Christophe , Lotz Jean-Pierre , Abadie Lacourtoisie Sophie , Fabbro Michel , Desauw Christophe , Bonichon Nathalie , Kurtz Jean Emmanuel , Follana Philippe , Leheurteur Marianne , Del Piano Francesco , Alliot Carol René , De Rauglaudre Gaetan , Ray-Coquard Isabelle Laure , Combe Pierre , Chevalier Annick , Joly Florence , You Benoit 
Published: May 2019

5546 Background: A pre-operative predictive biomarker of CC0 interval debulking surgery (IDS) likelihood would be helpful. The modeled CA125 elimination rate constant KELIM predicts OS in 1st line setting (You et al. Clin Cancer Res 2019). The predictive/prognostic values of KELIM regarding CC scores at IDS, and survivals, during neo-adjuvant chemotherapy were assessed. Methods: The data of the CHIVA randomized phase II trial, comparing carboplatin-paclitaxel +/- nintedanib before IDS (NCT01583322), were used. A semi-mechanistic model was built to describe CA125 longitudinal kinetics during the first 100 treatment days. The relationships between KELIM and IDS CC scores, PFS & OS, were assessed with other major prognostic factors (grade, histology, GCIG CA125 response, FIGO stage, and arm) using multivariate logistic regression (logit), C-index & survival tests. Results: The longitudinal kinetics of 529 CA125 values, assessed every 3 weeks during neo-adj chemotherapy, were modeled in 133 patients (out of 188). KELIM (as a continuous covariate) was the only significant predictive factor of CC0 IDS likelihood using multivariate analyses (OR = 12.37, 95% CI [4.32-39.67]). CC0 IDS probability can be estimated with patient KELIM: ≥ 90 % if standardized KELIM ≥ 0.12. Non-parametric survival models confirmed the independent predictive values of KELIM categorized by terciles regarding PFS & OS (Table). The parametric model linking KELIM (as a continuous covariate) with OS allows to predict the patient survivals (months) based on their estimated KELIM (HR = 0.20, [0.10-0.39]). Conclusions: The prognostic & predictive values of the modeled CA125 KELIM are also confirmed regarding CC0 IDS likelihood, PFS and OS with neo-adjuvant chemotherapy. Patient KELIM is calculable online, based on observed CA125 values, on http://www.biomarker-kinetics.org/ . Clinical trial information: 2011-006288-23. [Table: see text]
Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) 50 mg/m2 and 40 mg/m2 in patients with platinum-resistant Müllerian carcinoma (JGOG3018).
Authors: Yabuno Akira , Tabata Tsutomu , Michimae Hirofumi , Oishi Tetsuro , Nonaka Miwa , Takano Masashi , Hirata Toru , Fujiwara Keiichi , Sugiyama Toru 
Published: May 2019

5550 Background: The standard dose of single-agent pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks, but 40 mg/m2 has recently been used in clinical practice, though there is no evidence available to support its use. Methods: A Phase III, randomized, multicenter, non-inferiority study comparing progression-free survival (PFS) of patients with platinum-resistant Mullerian carcinoma (epithelial ovarian, fallopian tube, or primary peritoneal carcinoma) treated with an experimental arm (40 mg/m2 PLD) versus a standard arm (50 mg/m2 PLD) until 10 courses, disease progression, or unacceptable toxicity was conducted. Eligible patients had ≤ 2 prior lines. Stratification was by performance status (PS) and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS, and secondary endpoints were overall survival (OS), toxicity profile, clinical response, and tolerability. The target total number of patients was 412. Results: The trial was closed due to accrual futility as patient recruitment was slow , with 272 patients randomized to the experimental arm (n=137) and the standard arm (n=135). The final analysis was performed with 234 deaths and 269 events for PFS. Median patient age was 62 years; 58% of patients had a treatment-free interval less than 3 months, and 81% of patients had PS 0. In the experimental versus standard arm, median PFS was 4.0 months versus 4.0 months (HR 1.065, 95.8%CI: 0.830-1.366), and median OS was 14.0 months versus 14.0 months (HR 1.078, 95%CI: 0.831-1.397). Adverse events ≥Grade 2 including oral cavity mucositis were more frequent in the standard arm than in the experimental arm (26.7% vs. 13.5%, respectively; p=0.0089), but there was no difference in ≥Grade 2 hand-foot-skin reactions (19.8% vs. 15.0%, respectively; p=0.333). Conclusions: The non-inferiority of PFS with the reduced dosing schedule was not confirmed because the trial was closed prematurely, but PFS and OS were similar. These results suggest a reduction of the standard dose of PLD because of the low rate of oral mucositis in patients with platinum-resistant ovarian cancer treated with the lower dose regimen. Clinical trial information: UMIN000003130.
Bevacizumab or PARP-inhibitors maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer (rOC)? A network meta-analysis (NMA).
Authors: Bartoletti Michele , Pelizzari Giacomo , Gerratana Lorenzo , Garattini Silvio Ken , Basile Debora , Lisanti Camilla , Bortot Lucia , Corvaja Carla , Garutti Mattia , Scalone Simona , Nicoloso Milena , Bolzonello Silvia , Torrisi Elena , Da Ros Lucia , Di Nardo Paola , Lombardi Davide , Giorda Giorgio , Baldassarre Gustavo , Sorio Roberto , Puglisi Fabio 
Published: May 2019

5564 Background: Patients (pts) experiencing a PS rOC are generally re-exposed to a platinum based-chemotherapy (CT). In this setting, the addition of a targeted agent like bevacizumab (BEV) or PARP inhibitors (PARPi) as concomitant and/or maintenance therapy has shown to improve progression free survival (PFS). In the absence of direct comparison in randomized trials (RCTs), we have performed a NMA to evaluate differences in terms of efficacy between BEV and PARPi in pts with PS rOC, according to BRCA status. Methods: We searched PubMed, Embase and Medline for RCTs involving pts with PS rOC treated with BEV (n = 3, 1563 pts) or PARPi (n = 5, 1839 pts). Only trials with PFS as primary endpoint were included. Trials in first line setting were excluded. Analyses have been done pooling pts who had received PARPi in three groups, according to the available data on BRCA genes status: all comers (AC), BRCA mutated pts (BRCAm) and BRCA wild-type pts (BRCAwt). A frequentist approach has been used with R statistical software. To rank the effect size of treatments, surface under the cumulative ranking value (SUCRA) has been applied. Results: In AC pts, PARPi improved PFS compared to BEV (hazard ratio [HR] = 0.70, 95% CI 0.54-0.91, test of heterogeneity [I2] = 40.5%). In BRCAm pts the gain in PFS for PARPi was even higher compared to BEV (HR = 0.46, 95% CI 0.36-0.59, I2= 17.2%). In BRCAwt pts the benefit of PARPi over BEV was not statistically significant (HR = 0.87, 95% CI 0.63-1.20, I2= 35.7%) but PARPi had the highest likelihood of being ranked as the best treatment in terms of efficacy according to SUCRA (90% and 60%, respectively for PARPi and BEV). Hazard ratio for PFS between PARPi, BEV and CT in the three cohorts are reported in the table. Conclusions: According to indirect comparisons, PARPi performed the best for the treatment of PS rOC, especially in BRCAm pts who had not previously received PARPi. BEV could be still an option in BRCAwt pts. [Table: see text]
Rethinking breast cancer surveillance in women with BRCA-associated ovarian cancer in the post-solo trial era.
Authors: John Catherine S. , Amersi Farin F. , Fong Abigail , Gillen Jessica , Moore Kathleen N. , Walsh Christine S. , Li Andrew John , Rimel Bj , Cass Ilana 
Published: May 2019

5565 Background: Patients with BRCA mutations are at increased risk of developing both breast (BC) and epithelial ovarian cancer (EOC). Optimal breast cancer surveillance guidelines for BRCA mutation carriers following EOC has not been defined due to high risk of EOC recurrence. The recent SOLO-1 trial demonstrated a survival benefit of olaparib maintenance therapy for newly diagnosed women with advanced stage EOC. Olaparib reduced the risk of disease-progression or death by 70% compared to placebo with a median progression-free survival (PFS) of 36 months. Methods: An IRB-approved, multi-institutional study retrospective chart review was performed. Patients had BRCA-associated EOC diagnosed between 1990-2015 without a history of prior BC or mastectomy. All women received combination chemotherapy for EOC. The observed breast cancer free survival was adjusted to reflect the enhanced 3-year PFS observed in olaparib-treated women from the SOLO-1 trial. Kaplan-Meier survival curves were performed. Results: 191 patients with BRCA-associated EOC were included (135 BRCA1, 55 BRCA2, 1 BRCA1 and BRCA2). Median age was 53 years. Most women had advanced stage, high-grade serous EOC (75%). The median overall survival was 7.7 years for BRCA 1, and 9.7 years for BRCA2 mutation carriers. Annual mammography and MRI were performed in 43% and 34% of women, respectively, with a median of 4 mammograms and 3 MRI per patient. 16 women (8.3%) were diagnosed with BC over a median follow up of 80 months: 7 (44%) DCIS and 9 (56%) invasive ductal carcinoma. 14 (88%) women had early stage (0-2) BC. 28 (15%) of women had risk-reducing mastectomy performed an average of 2.1 years following their EOC diagnosis. The incidence of BC increased from 5.6% to 11% at 5- and 10-years post EOC, and in the predicted model with olaparib, from 10% to 17% at 5- and 10-years, assuming olaparib does not impact breast cancer incidence. Conclusions: The risk of metachronous BC following BRCA-associated EOC increases over time. In the post SOLO trial era, BC surveillance strategies in women with EOC should be optimized to reflect improved outcome. [Table: see text]
Multi-parametric FDG PET/MRI as an early predictor of response to neoadjuvant chemotherapy in patients with epithelial ovarian cancer.
Authors: Frey Melissa Kristen , Sawaged Zacharia , Franceschi Ana M , Friedman Kent P , Lutz Kathleen , Curtin John Patrick , Blank Stephanie V. , Pothuri Bhavana 
Published: May 2019

5569 Background: For patients with ovarian cancer undergoing neoadjuvant chemotherapy, the effectiveness of treatment is not evaluable by conventional methods until all or much of the treatment has been given. The purpose of this study is to investigate the performance of FDG PET, dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR as early predictors of treatment response. Methods: Subjects with a new diagnosis of epithelial ovarian cancer underwent 3 cycles of standardized chemotherapy followed by cytoreduction. FDG PET/MR including DCE and IVIM was performed at baseline (T0), after cycle 1 (T1) and after cycle 3 (T2) of chemotherapy. Final responses were categorized at T2 by RECIST 1.1. Image volumes at T1 were analyzed as predictors of final response. Parametric images of molecular diffusion restriction (D), tissue perfusion (D*), vascular volume fraction (F), blood- > interstitium constant of transfer (Ktrans), interstitum- > plasma constant of transfer (Kep), extravascular/extracellular volume % (Ve) and plasma volume % (Ve) were investigated along with routine measures of SUV and ADC. Results: Nine subjects were enrolled, 8 were responders by RECIST at T2 and one had stable disease. At T0 the mean, min, and max SUVmax of dominant tumor deposits was 11.5, 6.3, 19.0, respectively. Mean, min, and max values were 1.0, 0.75 and 1.63 for ADCmean and 0.62, 0.30, 0.96 for ADCmin. At T1, ADCmean increased in 8 subjects by +0.22% (s.d. +/- 13%) and decreased by -3% in one subject. ADCmin increased in 8 subjects by +21% (s.d. +/-11%) and decreased by -23% in one subject. D increased for 8 subjects (average +29% s.d. +/- 13%) and decreased by -10% in one. D*, F, Kep, Ktrans, Ve and Vp had no recognizable pattern. At T2, SUVmax, SUVmin, and ADCmean maintained their change direction across all subjects with measurable lesions. The only subject with a complete response at T2 had the highest ADCmin and ADCmean change at +45% after one cycle of chemotherapy (T1). The subject with stable disease at T2 had no significant difference in changes amongst all metrics. Conclusions: FDG PET/MR SUVmax and ADCmean values obtained after one cycle of neoadjuvant chemotherapy were consistently associated with partial anatomical treatment responses after three cycles. Molecular diffusion restriction also was reliably associated with treatment response. Future studies evaluating FDG PET/MR in platinum-resistant patients may allow for early discontinuation of ineffective and toxic treatment.
A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma.
Authors: Rubinstein Maria M , Caird Imogen , Zhou Qin , Iasonos Alexia , Friedman Claire Frances , Cadoo Karen Anne , Konner Jason A. , O'Cearbhaill Roisin Eilish , Tew William P. , Zamarin Dmitriy , Grisham Rachel N. , Kyi Chrisann , Soldan Krysten , Lichtman Stuart M. , Ligresti Louise , Schweber Sarah J. , Singh Jasmeet Chadha , Troso-Sandoval Tiffany A. , Aghajanian Carol , Makker Vicky 
Published: May 2019

5582 Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS24wks) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129.