bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Overall survival (OS) results from the phase II LIGHT study.
Authors: Mathews Cara Amanda , Simpkins Fiona , Cadoo Karen Anne , Liu Ying L , Provencher Diane M. , McCormick Colleen , ElNaggar Adam , Altman Alon D , Gilbert Lucy , Black Destin , Kabil Nashwa , Bennett James , Munley Jiefen , Yu Judy , Aghajanian Carol 
Published: June 2021

5515 Background: LIGHT (NCT02983799) evaluated olaparib Tx in pts with PSR OC in cohorts with known BRCAm and HRD status. We report the final OS analyses. Methods: We conducted anopen-label, non-randomized, multicenter study of pts with PSR OC and ≥1 prior line of platinum-based chemotherapy (CTx). Pts were assigned to one of 4 cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD +ve (non-BRCAm); and HRD -ve. Genomic instability score (GIS) and gBRCAm status were determined by Myriad myChoice and BRACAnalysis CDx tests, respectively. HRD +ve tumors were defined by a GIS ≥42. Pts received olaparib Tx (starting dose 300 mg bid) until disease progression or unacceptable toxicity. OS was a secondary endpoint and was analyzed at 12 months (mo) after the primary analysis and 18 mo after the last pt was enrolled. Safety was assessed in pts who received ≥1 dose. Results: Data cut-off (DCO) was Aug 27, 2020. Of 272 enrolled pts, 271 received olaparib; of these, 270 had measurable disease at baseline and were included in efficacy analyses (Table). At DCO, 40% of pts had died (maturity) with a median follow-up in censored pts of 26.3 mo. Kaplan–Meier 18-mo OS rates were 86%, 88%, 79%, and 60% in the gBRCAm, sBRCAm, HRD +ve (non-BRCAm), and HRD -ve cohorts, respectively. Platinum-based CTx was the most common first subsequent Tx and was received by 39% pts after olaparib discontinuation. At DCO, the median duration of Tx was 7.4 mo and 244 pts had discontinued treatment, mainly due to disease progression (72%); 5% discontinued due to treatment-emergent adverse events (TEAEs). The only TEAE leading to discontinuation in >1 pt was nausea (2 pts). Serious TEAEs were reported in 25% of pts. The most common serious TEAE was small intestinal obstruction (6%). Three adverse events of special interest occurred, each in 1 pt (<1%): acute myeloid leukemia (post discontinuation), pneumonitis, and pulmonary fibrosis. Conclusions: In the final OS analysis, 18-mo OS ranged from 60–88% across the 4 cohorts. Consistent with the primary analysis, the 18-mo OS rate was highest in the BRCAm cohorts (similar OS in g and sBRCAm); among pts without a BRCAm, 18-mo OS was highest in the HRD +ve cohort. No new safety signals were observed compared with the primary analysis and with prior olaparib studies. Clinical trial information: NCT02983799. [Table: see text]
Anlotinib plus sintilimab in patients with recurrent advanced cervical cancer: A prospective, multicenter, single-arm, phase II clinical trial.
Authors: Xu Qin , Chen Chuanben , Sun Yang , Huang Zhangzhou , Lin Yibin , Liu Jing , Li Li , Li Zirong , Pan Junping , Chen Ying 
Published: June 2021

5524 Background: It is difficult for patients with recurrent advanced cervical cancer to obtain clinical benefits after the failure of standard chemotherapy. However, antiangiogenic therapy combined with immune checkpoint inhibitors have become a promising strategy for advanced cervical cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. Sintilimab is a fully humanized, high-affinity monoclonal antibody against programmed cell death-1 (PD-1). This phase II, single-arm study (ChiCTR1900023015) aims to evaluate the efficacy and safety of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer. Methods: Patients who have received at least once platinum-based chemotherapy, histopathologically confirmed recurrent advanced cervical cancer (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), more than 1% PD-L1 expression, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg once every 3 weeks). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2019 and February 2021, 42 patients with a median age of 52 years (range:47-58), FIGO histopathological stage I (11.9%), II (31.0%), III (33.3%), IV (9.5%) and undiagnosed (14.3%) were enrolled. 39 of these patients were evaluable. In the efficacy-evaluable population (n = 39), the therapeutic evaluation showed that 2 and 20 patients achieved complete response and partial response respectively, yielding the ORR of 56.4% (22/39, 95% CI:40.2 to 71.5). The DCR was 94.9% (37/39, 95% CI:80.7 to 98.8). The median response time was 1.6 months. The median PFS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypothyroidism (33.3%), hypertension (23.8%), AST (21.4%), diarrhea (19.0%), ALT (16.7%), hand-foot syndrome(14.3%), hypertriglyceridemia (14.3%) and anemia (11.9%). The grade 3 AEs were hypertension (4.8%), hyponatremia (4.8%), immune pneumonia (2.4%) and immune myocarditis (2.4%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for patients with recurrent advanced cervical cancer. We will report more data in the future. Clinical trial information: ChiCTR1900023015.
A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.
Authors: Jackson Camille Catherine , Cantrell Leigh , Erickson Britt Kristina , Moore Kathleen N. , Duska Linda R. , Richardson Debra L. , Landrum Lisa Michelle , Holman Laura L. , Walker Joan L. , Mannel Robert S. , Moxley Katherine M. , Queimado Lurdes , Ding Kai , Cohoon Andrew , Vesely Sara , Dockery Lauren E. 
Published: June 2021

5527 Background: Treatment options for patients with recurrent cervical and endometrial cancer remain limited. Even with optimum care, median survival has stalled at 12-17 months. The PARP inhibitor rucaparib has demonstrated activity in both BRCA wild-type and mutant cancers. Furthermore, preclinical studies suggest a synergistic effect of PARP inhibitors and antiangiogenic agents. We hypothesized that the combination of rucaparib and the VEGF inhibitor bevacizumab would yield a clinically-significant anti-cancer effect in patients with persistent or recurrent cervical or endometrial carcinoma. Methods: NCT03476798 is a phase II trial of adults with histologically-documented carcinoma of the cervix or endometrium. Patients with evaluable lesions who had undergone at least one prior line of systemic therapy, had adequate performance status and organ function, with a life expectancy of at least three months were eligible. Biopsies were obtained prior to treatment initiation for assessment of baseline tumor biomarkers, including ARID1A mutation status. Each cycle comprised 21 days. Rucaparib was administered orally at 600 mg, twice daily. Bevacizumab was administered by IV at 15 mg/kg on day 1 of each cycle. The primary objective was to estimate the proportion of patients with persistent or recurrent cervical or endometrial cancer who survive progression-free for at least six months (PFS6). Kaplan-Meier analysis was used to estimate progression-free survival. Results: There were 28 evaluable patients; six had cervical and 22 had endometrial cancer. Median age was 60.5 years (range, 30-74). Self-reported patient races were White (82.1%), Black (10.7%), and Native American (7.1%). Self-identified Hispanic or Latina patients comprised 3.6% of the cohort. Twenty-two of 28 patients had progressive disease by six months [survival distribution function estimate = 0.214 (lower CI, 0.087; upper CI, 0.378)]. Of the six patients who achieved PFS6, one had cervical and five had endometrial cancer. Six patients had a mutation in the ARID1A gene and those patients achieved PFS6 at a rate of 66.7%. Conclusions: The study hypothesis was evaluated in a two-stage design, and the interim analysis occurred once 28 evaluable patients were enrolled. In order to move on to the second stage, at least seven patients needed to remain progression-free at six months, but only six did. Thus, the study was ended after the interim analysis. The combination of rucaparib and bevacizumab did not provide the expected clinical benefit in this cohort of patients, but may warrant further exploration in patients with ARID1A mutations. Clinical trial information: NCT03476798.
Safety assessment of niraparib individualized starting dose in patients with platinum-sensitive recurrent ovarian cancer: A randomized, double-blind, placebo-controlled, phase III NORA trial.
Authors: Wang Jing , Wu Xiaohua , Zhu Jianqing , Yin Rutie , Yang Jiaxin , Huang Qidan , Wu Lingying , Liu Ziling , Gao Yunong , Wang Danbo , Lou Ge , Yang Hongying , Zhou Qi , Kong Beihua , Huang Yi , Chen Lipai , Li Guiling , An Ruifang , Tan Tao , Dong Juan 
Published: June 2021

5535 Background: To present the safety profile of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer (PSROC) included in the NORA trial. Methods: The double-blind, randomized, placebo-controlled, multicenter, phase III NORA trial (NCT03705156) included adult (≥18 years) Chinese women with PSROC who received ≥2 prior lines of platinum-based chemotherapy. Post ≤8 weeks of the last chemotherapy, patients were randomized (2:1) to receive oral niraparib (300 mg/day or 200 mg/day for patients with bodyweight <77 kg or platelet count <150 × 103/µL) or matched placebo. The primary endpoint was progression free survival, reported previously. Safety was assessed in terms of treatment emergent adverse events (TEAEs) related to hematologic toxicity (anemia/platelet count decreased and neutrophil count decreased) and non-hematologic toxicity (nausea/vomiting/constipation/insomnia/palpitations/hypertension). Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The data cutoff was February 1, 2020. Results: Of 265 patients included, the first 16 patients were given oral niraparib or matched placebo at a fixed starting dose of 300mg while 249 patients received individualized starting dose of niraparib (n = 166) or matched placebo (n = 83) based on baseline bodyweight and platelet count. The incidence of any TEAEs and grade ≥3 TEAEs was 100% and 50.8%, respectively in niraparib group, while 95.5% and 19.3%, respectively in placebo. Incidence of all grades of hematologic toxicity, gastrointestinal adverse events (nausea, constipation and vomiting), insomnia, palpitation and hypertension were highest in the first month after treatment with a gradual decrease in the further months. The median time to onset of grade ≥3 anemia, decreased neutrophil count and decreased platelet count were 87, 28, and 22 days, respectively, in the niraparib group. In niraparib group, any TEAEs that lead to dose reduction was observed in 59.9% of patients. Only 2 (1.1%) patients discontinued the treatment due to platelet count decreased and no patients discontinued niraparib treatment due to anemia or neutrophil count decreased. Overall, only 4% of patients in the niraparib group and 5.7% in the placebo group discontinued the treatment due to TEAEs. Conclusions: The lower incidence of TEAEs and the discontinuation rates indicate improved safety profile of niraparib with individualized starting dose in PSROC. Clinical trial information: NCT03705156.
Trends in the incidence of endometrial cancer among young women in the United States, 2001 to 2017.
Authors: Guo Fangjian , Levine Lyuba , Berenson Abbey 
Published: June 2021

5578 Background: Endometrial cancer at this time is predominantly being looked at as a disease of postmenopausal population. Increased obesity has been identified as an important risk factor for endometrial cancer. An overall increase incidence of endometrial hyperplasia and endometrial carcinoma in obese premenopausal women has been reported. A close examination of the relationship between trends in endometrial cancer incidence and obesity prevalence in young women will provide important information for prevention and early screening of the disease and its precursors. This study was to assess current trends in endometrial cancer incidence in women ages 20-29 and 30-39 years in relationship to obesity in the US. Methods: We used data on US adult women 20-39 years old from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence–U.S. Cancer Statistics 2001–2017 database. This database covered essentially all young female population between 2001 and 2017 in the US (Puerto Rico not included). Incidence was age adjusted to the 2020 U.S. standard population. We also examined the trends in obesity prevalence among females 18-34 years old using data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Results: There were 24,446 cases of endometrial cancer among young adult women aged 20-39 years during 2001-2017. Endometrial cancer incidence increased from 0.6 per 100,000 in 2001 to 1.2 per 100,000 in 2017 (APC 3.6, 95% CI 2.9-4.4) among young women 20-29 years old, and increased from 4.6 per 100,000 in 2001 to 7.5 per 100,000 in 2017 (APC 3.0, 95% CI 2.7-3.3) among women 30-39 years old. Obesity prevalence also increased significantly from 1988-2014 among females 18-34 years old. Incidence of endometrial cancer and obesity prevalence were both higher in Hispanics than in other racial/ethnic groups. Conclusions: The significant increasing incidence in endometrial cancer among young adult women is in accordance with the concurrent increasing prevalence in obesity in young girls and women in the US. This indicates that endometrial cancer screening might need to be considered at much earlier age among patients with abnormal bleeding and certain ethnic populations.
Computational features of TIL architecture are differentially prognostic of uterine cancer between African and Caucasian American women.
Authors: Azarianpour Esfahani Sepideh , Fu Pingfu , Mahdi Haider , Madabhushi Anant 
Published: June 2021

5585 Background: Although the vast majority of endometrial cancer (EC) is early-stage and thus, curable by surgery, chemotherapy, and radiotherapy (with at least 85% 5-year OS), a fraction of them are aggressive neoplasms such as high-grade or deeply invasive lesions and thus exhibit poor prognosis. African American (AA) women are disproportionately affected by high-grade EC and have 80% higher mortality rate compared with Caucasian American (CA) women. In this work, we evaluated the prognostic ability of computational measurements of architecture of tumor-infiltrating lymphocytes (ArcTIL) from H&E slide images for EC. We also investigated the presence of morphologic differences in terms of ArcTIL features between AA and CA women and whether ArcTIL based population-specific models were more prognostic of OS in AA women compared to a population-agnostic model. Methods: The study included digitized H&E tissue slides from 445 post-surgery EC patients from TCGA, with further chemotherapy, or radiotherapy, including only the AA and CA patients, patients without reported race or from other populations were excluded. The dataset was divided into discovery (D1, n = 300), and a validation set (D2, n = 145), while ensuring population balance between two splits (D1(AA) = 65, D1(CA) = 235, D2(AA) = 37, D2(CA) = 108). A machine learning approach was employed to identify tumor regions, and tumor-associated stroma on the diagnostic slides and then used to automatically identify TILs within these compartments. Graph network theory based computational algorithms were used to capture 85 quantitative descriptors of the architectural patterns of intratumoral and stromal TILs. A multivariable Cox regression model (MCRM) was used to create population specific-prognostic models (MAA, MCA) and a population-agnostic model (MAA+CA)) to predict OS. All 3 models were evaluated on D2(AA), D2(CA), and D2. Results: MAA identified 4 prognostic features relating to interaction of TIL clusters with cancer nuclei in stromal compartment and was prognostic of OS on D2(AA) (see Table) but not prognostic in D2(CA) nor D2(AA+CA). MCA and MAA+CA identified respectively 7 and 6 prognostic features relating to interaction of TIL clusters with cancer nuclei (both in the epithelial and stromal regions) and were prognostic of OS on D2(CA) and D2, but not prognostic in D2(AA). Conclusions: Our findings suggest an important role of stromal TIL architecture in prognosticating OS in AA women with EC, while epithelial TIL features were more prognostic in CA women. These findings need to be validated in larger, multi-site validation sets.[Table: see text]
Association of the presence of estrogen and progesterone receptors in uterine carcinosarcoma with improved survival and increased immunogenicity.
Authors: Jones Nathaniel L. , Wu Sharon , Xiu Joanne , Rocconi Rodney Paul , Erickson Britt Kristina , Thaker Premal H. , Brown Jubilee , Herzog Thomas J. , Holloway Robert W. , Korn Wolfgang Michael , Powell Matthew A. , Wilhite Annelise M. 
Published: June 2021

5588 Background: Recent data has shed light on molecular profiles of uterine carcinosarcoma (UCS), but few have correlated molecular profiles with prognosis. In a preliminary data analysis, we found that hormone receptors (HR)—estrogen receptor (ER) and progesterone receptor (PR)—expression was associated with improved OS. Here, we investigate the molecular profile differences between ER+/- and PR +/- tumors. Methods: Tumor samples were analyzed using Next-Generation sequencing of DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing) and RNA (NovaSeq, whole transcriptome sequencing) and immunohistochemistry (IHC) at the Caris Life Sciences Laboratory (Phoenix, AZ).ER and PR tested by IHC on whole tumor (cut-off: +1, 10%). PD-L1 IHC used SP-142 (cut-off >1%). MSI was tested by FA, IHC an NGS. TMB was measured by totaling somatic mutations per tumor (high > 10 mutations per MB). Immune cell fraction was calculated by QuantiSeq. Overall survival (OS) information was obtained from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Statistical significance was determined by chi-square and Wilcoxon rank sum test and p-values adjusted for multiple comparisons (q) to be <0.05. Results: 1,144 UCS tumors were included. (ER+, n=261; PR+, n=197; HR+ (ER+ and PR+), n=168). Median OS for patients with hormone receptor (HR)+ tumors was significantly longer than for patients with HR- tumors (months: 34.8 vs 17.4; HR(95% CI): 0.67 (0.53-0.84), p<0.01). This remained significant for ER (29.4 vs 17.3) and PR (25.3 vs 18.7) individually. ER+ tumors had fewer alterations in the TP53 pathway (71.4% vs 82.1%) in the WNT (19.5% vs 5.8%) pathway than ER- tumors (q<0.05). PR+ tumors had similar findings in the TP53 and WNT pathways, and also more alterations in the DNA damage sensor pathway. Both ER+ and PR+ UCS tumors had significantly increased MSI-H (ER: 10.9% vs 5.5%, PR: 12.9% vs 5.5%) and TMB-H (ER: 16.8% vs 6.0%; PR: 19.5% vs 6.1%) (all q<0.05) compared to ER- and PR- tumors. They also had increased T-reg cells in their immune micro-environment and increased expression of the immune checkpoint gene IDO1 (q<0.05; Table). Conclusions: HR+ tumors have distinct molecular profiles from HR- tumors. ER+ and PR+ UCS tumors appear more immunogenic with more frequent MSI-H status, TMB-H, increased infiltrating regulatory T-cells and IDO1 expression, suggesting possible benefit with immune-oncology (IO) therapy. This may contribute to the observed improved OS, but more data are needed to determine if HR status is a marker of response to IO therapy.[Table: see text]
Adding carbon nanoparticles to dual-tracers for the sentinel node evaluation after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers: The TT-SLNB trial.
Authors: Chen Jie , Yang Jiqiao , He Tao , Wu Yunhao , Jiang Xian , Fu Zhoukai , Lv Qing , Lu Shan , Wang Xiaodong , Li Hongjiang , Wang Jing 
Published: June 2021

566 Background: This study measures the feasibility and accuracy of sentinel lymph node biopsy (SLNB) with triple-tracers (TT-SLNB) which combines carbon nanoparticles (CNS) with dual tracers of radioisotope and blue dye, hoping to achieve an optimized method of SLNB after neoadjuvant chemotherapy (NAC) in ycN0 breast cancer patients with pretreatment positive axillary lymph nodes. Methods: Clinically node-negative invasive breast cancer patients with pre-NAC positive axillary lymph nodes who received surgeries from November 2020 to January 2021 were included. CNS was injected at the peritumoral site the day before surgery. Standard dual-tracer (SD)-SLNs were defined as blue-colored and/or hot nodes, and TT-SLNs were defined as lymph nodes detected by any of hot, blue-stained, black-stained, and/or palpated SLNs. All patients received subsequent axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were calculated. Results: Seventy-six of 121 (62.8%) breast cancer patients converted to cN0 after NAC and received TT-SLNB. After NAC, 28.95% (22/76) achieved overall (breast and axilla) pCR. The DR was 94.74% (72/76), 88.16% (67/76) and 96.05% (73/76) for SLNB with single-tracer of CNS (CNS-SLNB), SD-SLNB, and TT-SLNB, respectively. The FNR was 22.86% (8/35) for CNS-SLNB and 10% (3/30) for SD-SLNB. The FNR of TT-SLNB was 5.71% (2/35), which was significantly lower than those of CNS-SLNB and SD-SLNB. The NPV and accuracy was 95.0% and 97.3% for TT-SLNB, respectively. Moreover, a significant relation was seen between the pretreatment clinical T classification and the DR of TT-SLNB (Fisher’s exact test, p= 0.010). Conclusions: TT-SLNB revealed ideal performance in post-NAC ycN0 patients with pretreatment node-positive breast cancers. The application of TT-SLNB reached a better balance between more accurate axillary evaluation and less intervention. Clinical trial information: ChiCTR2000039814. [Table: see text]