bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of carrying BRCA pathogenic mutations in ovarian cancer and its platinum-sensitivity: 5-year experience of a tertiary center.
Authors: Jiménez Labaig Pablo , Lombardero Lara , Rivero Maria Pilar , Mohamed Lamin Failah , Ortega Berezi , Miñambres Nagore , Fuente Natalia , Marrodan Ines , Iza Estibaliz , Carrera Sergio , Iruarrizaga Eluska , Sancho Aintzane , Rubio Itziar , Mañe Joan Manel 
Published: June 2022

e17572 Background: Platinum-based chemotherapy still remains as the backbone treatment in ovarian cancer (OC) and its homologous tumors (primary peritoneal PP and fallopian tube FT cancer). BRCA mutational status is a sensitivity predictor to platinum chemotherapy. The aim of this study is to quantify the benefit of carrying a BRCA mutation along the subsequent platinum treatments and beyond. Methods: A descriptive, retrospective, single center study was developed in a tertiary hospital. OC, PP and FT neoplasms in stage III/IV, treated between 01/2015 and 12/2020 were included. Demographic characteristics, BRCA and HRD pathogenic mutational status, platinum-sensitive survival (PSS), platinum-resistant survival (PRS) and overall survival were analyzed. A p-value of < 0.05 was considered statistically significant. Results: 116 patients were recruited (96 OC, 9 PP, 7 FT). 100 were non-BRCA mutated (including 2 germline BRIP, 1 RAD51C), 16 were BRCA-mutated (8 germline BRCA1, 7 germline BRCA2, 1 somatic BRCA2). 83 (71.6%) were stage III at diagnosis and 33 (28.4%) stage IV. Histologically, 90 cases were serous subtype (77.6%), 40.5% were grade 3. Mean age was 62.1 years. 90 (77.6%) received oncological surgery (debulking or interval procedure). A table is annexed with demographic characteristics without unbalanced distribution.Between BRCA-mutated group and non-mutated, the mean of platinum-based treatments was 2.63 (range 1-7) vs 2.49 (1-8), median PSS 42,8 months (9.7-80.1) vs 24.5 (2-78.9) HR 0.27 (95% IC 0.07-0.88. Log rank p-value 0.019), median PRS 20.3 (16-24.9) vs 9 (1.3-67.4) HR 1.1 p-value 0.715, and overall survival of 43.4 (11.3-81.4) vs 29 (0.7-78.9) HR 0.8 p-value 0.083. In contrast, histology factors, tumor markers, type of performed surgery, maintenance treatments and nonplatinum treatments didn’t result in a significant benefit as being carrier of BRCA mutation showed. Conclusions: Our analysis confirms that the platinum sensitive survival is deeply depend on the BRCA mutational status, remaining the most beneficial prognostic and predictive factor in the operated III/IV stages.[Table: see text]
Burden of cremophor-related paclitaxel therapy on patients with ovarian cancer: A patient focused study from the United Kingdom, Germany, and Spain.
Authors: Brixner Diana , Holtorf Anke-Peggy , Bhatia Ayesha , Oak Bhagyashree , Dehipawala Sumudu , Whitcher Clive , McKinley Kate , Martin Kyle , Hadker Nandini 
Published: June 2022

e17576 Background: Cremophor EL (CrEL) is a solubilizer used in paclitaxel and is associated with side effects (i.e., hypersensitivity reactions, peripheral neuropathy). Current CrEL-containing therapies require long infusion times (2-4 hours) and pre-medication with steroids to manage these side-effects. However, the holistic burden of CrEL on patients is not well studied. This study aimed to characterize the burden associated with CrEL-paclitaxel treatment on patients with ovarian cancer, including clinical, safety, and quality of life (QoL) implications. Methods: This quantitative, Institutional Review Board (IRB) approved, cross-sectional survey of patients (≥18 years) who received ≥3 cycles of CrEL-containing paclitaxel within the prior 6 months was conducted in UK, Germany, and Spain in 2021. Data were collected via a web-enabled instrument including a screener, questionnaire, and validated Functional Assessment of Cancer Therapy (FACT)-Taxane scale. Results are reported overall for the 3 countries. Results: Of the 90 patients surveyed, the mean age was 38.8 years. Most patients reported improvement of QoL (77%), treatment effectiveness (77%), less need for pre-medications (74%), and manageable/less disruptive infusion times and schedules (71%) as extremely desirable treatment attributes. Prior to or during chemotherapy, 41% of patients reported receiving steroids. Most patients (71%) experienced 3-6 side effects related to ovarian cancer treatment. Of the patients that experienced neuropathy (27%), the side effect lasted for up to 1 week for 54% of patients, and over multiple cycles of treatment (> 3 weeks) for 13% of patients. Of the 82% of patients eligible to complete the FACT-Taxane scale, 62% were somewhat to very much bothered by the side effects of paclitaxel. Half of these patients reported tingling/numbness in their hands/feet, moderately or very often. Patients reported an average of 4.8 hours as the time taken for their travels to/from the infusion center and receive their medication. Additionally, 91% of patients needed caregiver support for an average of 16 hours per week. 51% of patients reduced their work hours due to treatment and 58% reported a substantial impact on work productivity. To cover treatment costs, 63% purchased supplemental insurance. Conclusions: The patient-reported burden of treatment associated with CrEL-containing paclitaxel is significant and complex. Multiple treatment side effects occur in most patients which are burdensome and can recur and/or persist with future treatment cycles. There is an unmet need for an effective therapy that reduces treatment burden for patients and improves tolerability through fewer side effects, a reduced need for premedication, and shorter infusion time.
ODALIE Study, a retrospective analysis of a real-life cohort of patients with de novo advanced high grade epithelial ovarian cancer treated with a first-line platinum- and taxane-based chemotherapy combined with bevacizumab.
Authors: Bétrian Sarah Lagarde , Penault Llorca Frederique , Pautier Patricia , Joly Florence , Ray-Coquard Isabelle Laure , Costaz Hélène , Sauterey Baptiste , Floquet Anne , De La Motte Rouge Thibault , Gourgou Sophie , Marchal Frédéric , Guillemet Cecile , Petit Thierry , Rouzier Roman , Simon Gaetane , Gladieff Laurence 
Published: June 2022

e17577 Background: PARP inhibitors (PARPi) demonstrated improvement in progression-free survival (PFS) following a first line platinum-based chemotherapy including bevacizumab for HRD-positive advanced ovarian carcinoma (OC) patients (pts) (PAOLA-1 study). We aimed to describe real-world (rw) clinical outcomes in patients with de novo high grade epithelial advanced ovarian cancer (HGEOC) treated with a first-line platinum- and taxane-based chemotherapy combined with bevacizumab. Methods: Using the Epidemiological Strategy and Medical Economics (ESME) Ovarian Cancer (OC) Data Platform [NCT03275298], a French EHR-derived database centralizing deidentified data of consecutive patients diagnosed and/or treated in 18 French comprehensive cancer centers since 2011, we identified all patients with de novo FIGO stage III/IV HGEOC diagnosed between 01 October 2012 and 31 January 2017, with a documented response to a first-line platinum-based chemotherapy and a maintenance treatment with bevacizumab ( PAOLA-like control group population). Data cut-off was 06 August 2020. Endpoints (overall survival, PFS and time to subsequent treatment) were estimated using the Kaplan-Meier method. Subgroups were analysed according to the BRCA-derived status. Results: Of 10,263 OC cases in the ESME-OC cohort, 382 patients, with a median follow-up of 47.8 months (CI 95% 44.4-49.1), were analysed. Median age was 61 years (q1-q3: 56-68). 290 pts (75.9%) had a FIGO stage III, 361 pts (94.5%) had at least one surgery, 141 (39.1%) and 210 (58.5%) of them had a primary cytoreductive surgery and an interval surgery respectively. BRCA deleterious mutations were present in 72 pts (22.3%). Median progression free survival was 23.2 months (CI 95% 20.9-24.8) in overall population and 25.3 months (CI 95% 19.7-23.8) in BRCA mutated pts, comparable to the control arm of PAOLA-1 when considering the difference in the PFS definition (from first CT versus from randomization in PAOLA study). Estimated 24-months overall survival rate was 45.7% (95% CI: 40.7- 50.7) and 53.9% (95% CI: 42.4 - 65.5) in BRCA mutated pts. Conclusions: Analyses of our large real-world French ESME-OC cohort are powerful tools to confirm clinical outcomes in HGEOC pts. Our data confirmed the reproducibility of the results observed in randomized clinical trials for de novo HGEOC pts with a documented response to a first line with bevacizumab maintenance therapy.
Analytical evaluation of a commercial in-house homologous recombination deficiency (HRD) assay for patients with epithelial ovarian cancers and its concordance with a reference standard.
Authors: Ranghiero Alberto , Rappa Alessandra , Vacirca Davide , Colombo Nicoletta , Guerini Rocco Elena , Barberis Massimo 
Published: June 2022

e17592 Background: Homologous recombination deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs) as approximately half of EOCs have molecular aberrations in homologous recombination repair (HRR) genes, including BRCA1/2 gene mutations. Poly ADP-ribose Polymerase inhibitors (PARPi) have reformed the management of BRCA1/2 mutant ovarian cancer patients and demonstrated activity also in tumor with HRD status. The evaluation of HRD together with BRCA1/2 gene alterations is nowadays critical to guide the therapy decision for all patients with EOC. Different methods to assessed HRD have been reported and different assays are being implemented in clinical practice. Here, we sought to evaluate the analytical validity of a commercial in house HRD assay as compared to a reference standard method. Methods: 59 consecutive case of EOCs were included in this study. DNA extracted from representative formalin-fixed paraffin-embedded (FFPE) tissue block of each case were subjected to next-generation sequencing (NGS) analysis of BRCA1/2 genes alterations and HRD status using the AmoyDx HRD Focus Panel (Amoy Diagnostics Ltd, Xiamen, Fujian, China). HRD status was assesses through AmoyDx Genomic Scar Score (GSS) considering the length, type and location of the genome-wide chromosomal copy number variation through SNP probes spread throughout the genome. Cases with a GSS > 50 were considered as HRD positive. For each case the same FFPE tissue block was sent to Myriad Genetic Laboratories for myChoice CDx testing as reference standard. Assay concordance was measured as positive (PPA), negative (NPA) and overall (OPA) percentage of agreement according to the different scores proposed by the manufacturers. Results: HRD status data were available for 52 (88.1%) and 56 (94.9%) samples considering in-house and reference standard assay, respectively, and 49 cases was available for concordance analyses. AmoyDx HRD Focus Panel identified 23/49 samples (46.9%) as HRD positive and 26 (53.1%) as HRD negative. The concordance of HRD status between AmoyDx HRD Focus Panel and myChoice CDx was 100% and 81,2% for positive (PPA) and negative (NPA) cases respectively, with an overall analytical concordance (OPA) of 87.8%. No discordance was seen in BRCA1/2 status between in-house and reference standard assay (OPA: 100%). Conclusions: The HRD status assessed by AmoyDx HRD Focus Panel is highly concordant with that obtained using the current standard reference method. Commercial in-house test may offer a cost-effective, reliable and robust alternative to the centralized assay for the evaluation of HRD status in patient with EOC.
The tumor immune microenvironment correlates with neoadjuvant chemotherapy response in high-grade serous ovarian cancer.
Authors: Zhu Lei , Cao Guangming , Hua Dingchao , Cui Lina , Zhao Xiaochen , Wang Shuzhen 
Published: June 2022

e17605 Background: Platinum-based neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) and adjuvant chemotherapy has been an established alternative for advanced epithelial ovarian cancer (EOC). The chemotherapy response score (CRS) has been applied to assess the efficacy of NACT in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess the effect of NACT on tumor immune microenvironment (TIME) of HGSOC, and the correlation between the TIME and CRS. Methods: All patients underwent NACT with IDS. Formalin-fixed paraffin-embedded tissue samples were collected from pretreatment biopsy specimens and the corresponding post-NACT surgical specimens. The densities and percentage of various cell populations within the TIME were analyzed by multiplex immunohistochemistry (3DMedcines Inc.), including specific tumor infiltrating lymphocytes (TILs) (CD8+T cell, FOXP3+CD4+Treg cell and CD20+B cell), tumor associated macrophages (TAMs), NK cells (CD56 dim and CD56 bright). Patients were divided into three groups according to CRS based on pathological reaction of surgical specimens: CRS1 shows no or minimal response, CRS2 shows moderate response and CRS3 usually shows complete or near-complete response. Statistical analyses were performed using GraphPad Prism 7.0. P < 0.05 was considered statistically significant. Results: A total of 25 HGSOC patients were enrolled in this study, 32% (8/25) of patients with CRS 1, 64% (16/25) with CRS 2, and 4% (1/25) with CRS 3. After NACT, patients with CRS 2 or 3 had a significant increase of the densities of CD20+B cells in stroma (pre-NACT 15.71/mm3 vs. post-NACT 87.82/mm3, p = 0.048). We also observed borderline significant increases of percentage of CD20+B cells, the densities and percentage of CD8+T cells in stroma after NACT (pre-NACT vs. post-NACT, 0.32% vs.1.54%, 56.35/mm3 vs. 311.35/mm3, 0.95% vs. 5.48%, respectively). Meanwhile, no significant change in CD4+T, TAMs and NK cells. In patients with CRS 1, we observed a significant increase of the densities and percentage of CD4+FOXP3+Treg in stroma (pre-NACT vs. post-NACT, 1.38/mm3 vs. 19.75/mm3, p = 0.01; 0.04% vs. 0.41%, p = 0.017, respectively), while CD8+T, CD20+B, TAMs and NK cells did not change significantly. Additionally, we found a significant difference in CD56 bright NK infiltration when comparing CRS 2 or 3 group with CRS1 group in post-NACT (0.5/mm3 vs.12/mm3, p = 0.049; 0.005% vs. 0.23%, p = 0.048). Conclusions: These data suggest immune infiltrate in TIME may serve as a biomarker to predict response to NACT in HGSOC. The infiltration of CD8+ T and CD20+ B cell was more pronounced in CRS2 or 3, while the enhanced infiltration of FOXP3+CD4+Treg cells is associated with immunosuppressive TIME and poor response (CRS1). The mechanism of lymphocyte regulation is not completely understood, thereby deserving further investigation.
Real-world outcomes and prognostic factors in uterine leiomyosarcom: A single center experience from India.
Authors: Palo Upasana , Roy Arunava , Ghosh Anik , Mondal Debapriya , Chakraborti Basumita , Bhaumik Jaydip 
Published: June 2022

e17620 Background: Uterine leiomyosarcoma (uLMS) is a rare and aggressive malignancy with dismal prognosis, often diagnosed incidentally after surgery for presumed benign disorders. There is a dearth of prospective data particularly in Indian women owing to its rarity. Published studies differ about prognostic factors, and the role of adjuvant treatment in uLMS. Methods: Prospectively maintained uterine cancer electronic database was used to include uLMS patients with adequate clinical information who underwent treatment between January 1, 2012 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were calculated for the entire population, while recurrence-free survival (RFS) was calculated for the patients who had curative intent treatment. Various potential prognostic factors were tested using univariate and multivariate analysis. Results: Among 44 identified patients of uLMS, 32 women with sufficient information were included in the study. Majority of the patients had early stage disease at diagnosis including 19 (59.4%) patients with FIGO stage I tumors. Twenty three (71.9%) patients were diagnosed incidentally after surgery. Curative intent treatment was offered to 26 patients (81.3%) while 6 (18.7%) patients had palliative treatment. Median tumor size was 9 cm (interquartile range [IQR] 7-15), and the median mitotic count was 16 per 10 high power fields (hpf) (IQR, 12-25). Eleven patients (34.3%) received adjuvant chemotherapy while 15 patients (46.9%) remained on surveillance. After a median follow-up of 63.8 months, 22 patients (68.8%) had disease recurrence and 23 (71.9%) patients had died. Lung was the most common site (64.3%) of recurrence, followed by bone (18.8%), and abdominal cavity (12.5%). The median PFS and OS for the whole population were 20.7 months (95% confidence interval [CI] 13.7 - 27.7) and 28 months (95% CI 19.7 - 36.3) respectively. The 5-year PFS estimate was 20% while the 5-year survival probability was 25%. Stage specific 5-year OS probabilities for stage I, II, III, and IV were 45%, 40%, 20%, and 8% respectively. Patients who received adjuvant chemotherapy had longer RFS than those who were observed after primary surgery (median 59·9 months [95% CI 19.5–100.3] vs 20.5 months [95% CI 15.8-25.3]; hazard ratio [HR] 0·13 [95% CI 0.02-0.85; p = 0·03). Lower stage (FIGO stage I-II) (HR 0.15 [95% CI 0.03-0.67]; p = 0.013), and lower mitotic count (< 15/10 hpf) (HR 0.13 [95% CI 0.03-0.61]; p = 0.01) were independent prognostic factors associated with better survival. Conclusions: This 10-year experience of uLMS from an Indian tertiary care cancer center shows poor survival across stages with a high rate of recurrence. Only stage and mitotic count were found to be independent prognostic factors. The finding of RFS benefit with adjuvant chemotherapy warrants larger prospective studies to evaluate the role of adjuvant therapy in uLMS.
Squamous metaplasia in endometrial cancer changing local hormonal tumor profile.
Authors: Kornienko Svetlana V. , Frantsiyants Elena M. , Bandovkina Valeria A. , Moiseenko Tatiana I. , Adamyan Meri L. , Chernikova Natalia V. , Poryvaev Yuriy A. , Tumanyan Sergey V. , Maksimova Natalia A. , Boyko Konstantin P. , Gurnak Viktor V. , Arzamastseva M. A. , Egorova Anna S. , Verenikina Ekaterina V. , Ardzha Anna Yu , Kit Oleg I. 
Published: June 2022

e17621 Background: An imbalance of sex hormones in endometrial cancer (EC) towards hyperestrogenism together with progesterone deficiency is considered to stimulate proliferation and suppress endometrial apoptosis. EC with squamous metaplasia is characterized by a more severe clinical course and the lack of an adequate response to standard treatment. The purpose of this study was to analyze the local hormonal profiles of tumors with squamous metaplasia in patients with obesity. Methods: The main group included 20 EC patients with squamous metaplasia, and control group included 35 patients with endometrioid adenocarcinoma: T1-3N0-1M0, mean age 64±3.2 years. Intact endometrial tissues were obtained during surgical treatment of patients with uterine fibroids (n = 20). All patients gave their written informed consent for the study. Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), estrogen receptors ERα and ERβ, progesterone receptor RP4 and androgen receptors RA were measured by ELISA in samples of tumor and peritumoral (PT) tissues. Statistical processing of results was performed using the Statistica 10. Results: Tumor tissues of patients with EC, regardless of the histological structure, showed higher levels of estrogens and androgens and their receptors, compared with the intact endometrium, without significant changes in levels of progesterone and its receptor. In the main group, compared with the control group, E1 levels in tumors were lower by 1.6 times, E2 by 1.3 times (p < 0.05), but T higher by 2.4 times, ERα by 1.7 times, ERβ by 1.5 times (p < 0.05). PT, compared with the intact endometrium, had lower levels of E1 and E2 by 2 times and 1.5 times, P4 by 5.1 times, and T was lower only in PT with squamous metaplasia by 2.8 times. Levels of all steroid hormone receptors in PT were higher, regardless of the histological type of tumors. In PT of the main group, levels of E1 were 1.3 times lower (p < 0.05) than in controls, P4 – by 2.2 times, T – by 2.8 times, RP4 – by 1.7 times and ERβ by 1.8 times (p < 0.05), but ERα was 3.2 times higher. Conclusions: Tumors with squamous metaplasia, compared with endometrioid adenocarcinoma, are characterized by an imbalance of steroid hormones towards the predominance of androgens, and ERα plays a dominant role among estrogen receptors. The tumor probably synthesizes sex steroids independently and also pumps them over from the surrounding area. At the same time, malignant endometrial tumors, regardless of their histological structure, are more saturated with estrogens, androgens and their receptors, compared with the intact endometrium.
Adjuvant chemotherapy followed by adjuvant radiotherapy for treatment of high risk endometrial cancers: A retrospective review.
Authors: Kulkarni Anjali , Le Tien , Babadagli Ege , Samant Rajiv 
Published: June 2022

e17626 Background: Endometrial cancer is the most common gynecologic malignancy in North America (1-3). Patients who are considered to be high risk for recurrence are commonly treated with a combination of adjuvant chemotherapy and radiation. However, the optimal sequence of these therapies has not been defined. The purpose of this study is to review our progression-free survival (PFS) outcomes and recurrence rates and compare to established outcomes in the literature. Methods: A retrospective chart review was performed on all patients diagnosed with endometrial cancer who received adjuvant chemotherapy and radiation between Jan. 1, 2005 to Dec. 31, 2017 at The Ottawa Hospital. Main inclusion criteria for the study were stage III endometrial cancers of any histology, stage I-II endometrial cancers with serous or clear cell histology and stage IV endometrioid adenocarcinomas of the endometrium. The primary outcome of interest is the overall progression-free survival (PFS), defined as the time from surgery to disease recurrence or death by any cause. Results: A total of 140 patients were included in the study. Of these, 52 (37.1%) had endometrioid histology, 75 (53.6%) had serous, and 11 (7.9%) had clear cell histology. Of the total sample, 41 (29.3%) were stage 1 at diagnosis, 24 (17.1%) were stage 2, 68 (48.6%) were stage 3 and 7 (5.0%) were stage 4. The median start time to chemotherapy was 49 days after initial surgery. 130 (92.9%) completed a total of 6 cycles of chemotherapy (majority treated with carboplatin and paclitaxel). 92% of the patients completed radiation following chemotherapy; majority received external beam radiation +/- a brachytherapy boost. Radiation was started withing 4-6 weeks of completing chemotherapy. 42 (30.0%) patients were diagnosed with a recurrence during the time of follow-up and 7 were diagnosed with progressive disease on treatment. Of the recurrences, 2 (4.8%) were local, 5 (11.9%) were locoregional, 8 (19.0%) were isolated para-aortic, and 27 (64.3%) were distant. The median follow-up time for our sample was 63.9 months. The median PFS and overall survival for our sample was not reached. The estimated mean 5 year PFS was 0.69 and OS was 0.66. Conclusions: Although radiation prevents locoregional recurrences, chemotherapy improves survival outcomes in locally advanced and aggressive histology endometrial cancer. Previous reported outcomes have been based on giving adjuvant radiation first, followed by chemotherapy (4,5). Our results demonstrate that giving adjuvant chemotherapy first and then delivering radiation after may be the optimal approach since it leads to survival outcomes that compare favourably with the published literature and very few locoregional relapses.