bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proactive assessment of patient reported outcomes in patients with ovarian cancer.
Authors: Madariaga Ainhoa , Sanchez-Bayona Rodrigo , Kasherman Lawrence , Estrada-Lorenzo Jose Manuel , Lheureux Stephanie , Manso Luis , Tolosa Ortega Pablo , Alva Bianchi Manuel , Lema Laura , Ciruelos Eva M , Valcarcel David , Oaknin Ana , Oza Amit M. 
Published: June 2023

5567 Background: Patient reported outcome (PRO) measures are key instruments to provide an evaluation of health outcomes from the patient's perspective. Assessment of PROs may help identify the nature, severity, and time course of symptoms of concern in patients with ovarian cancer. The ability to access this information in real-time, including changes over time, could improve patient safety and decision-making. Methods: This systematic review evaluated the proactive or real-time assessment of PROs in patients with ovarian cancer undergoing systemic therapy. Medline, Embase, and Cochrane databases were searched (up to February 2022), and prospective ovarian cancer studies (experimental or observational) that incorporated PROs (including quality of life) were included. Conference abstracts were excluded. Primary objective was to assess the frequency of studies incorporating proactive use of PROs. A secondary objective was to describe PRO reporting. Descriptive statistics were used. Results: 3,071 articles were screened, with 117 included in the final analysis. Studies were published between 1990-2022 and contained 35,735 patients (median 140 patients per study; inter-quartile range 58-415). Median time from patient enrollment initiation to study publication was 7 years (range 1-15). Most studies were experimental/clinical trials (n=93, 79%), followed by observational (n=23, 20%) and not reported (n=1; Table). Among experimental studies, 56% (52/93) were phase III, 35.5% (33/93) phase II, 6.5% (6/93) phase I or I/II trials and it was not reported in two. Therapeutic strategies were assessed in 98% (91/93) of experimental studies, being the most frequent one chemotherapy (n=53, 58%), followed by antiangiogenics and PARP inhibitors (n=8, 9%, each). Types of observational studies were descriptive 43.5% (10/23), cohort 26% (6/23), cross-sectional 22% (5/23), or other 9% (2/23). PROs were the primary objective in 7.5% (7/93) and 83% (19/23) of experimental and observational studies respectively. The table describes PRO reporting standards per type of study. PROs were assessed in real-time in 0.8% (1/117) of studies. Conclusions: Completion of PRO and quality of life questionnaires involve time and effort for patients with ovarian cancer. PRO questionnaire responses were only assessed in real-time in <1% of analyzed studies. Efforts should be made to incorporate proactive assessment of PROs to optimize patient care and safety. [Table: see text]
Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.
Authors: Silberman Jason , Bercow Alexandra , Gockley Allison Ann , Eisenhauer Eric L , Sisodia Rachel , Randall Thomas Christopher , Melamed Alexander , Bregar Amy 
Published: June 2023

5581 Background: Following the publication of randomized trials demonstrating its noninferiority, the use of neoadjuvant chemotherapy (NACT) for the treatment of advanced stage epithelial ovarian cancer has increased substantially in the United States. However, low-grade serous ovarian cancers (LGSOC) respond poorly to chemotherapy compared with high-grade serous carcinoma. For LGSOC, clinical guidelines favor surgical resection prior to adjuvant therapy. This study seeks to describe patterns and temporal trends in the use of NACT for LGSOC. Methods: This cohort study identified women treated for stage III or IV LGSOC in a Commission on Cancer accredited cancer program between January 1, 2004, to December 31, 2020. We fit Poisson regression models to evaluate temporal trends in the use of NACT and cytoreductive outcomes, and to identify factors associated with receipt of NACT. We considered age, race/ethnicity, Charlson Comorbidity Index, year of diagnosis, insurance status, income, facility type, census region, and stage as potentially associated with NACT. Due to the high rate of missingness in data describing cytoreductive outcomes after surgery, we undertook both multiply imputed and complete case analyses. Results: A total of 3,343 patients received treatment for LGSOC during the study period. The mean age at diagnosis was 54.8 year (SD 15.5) and most patients (82%) were white. The most commonly observed upfront treatment strategies were cytoreductive surgery followed by adjuvant chemotherapy (63.7%) and surgery without chemotherapy (19.2%). Treatment with NACT followed by interval cytoreductive surgery (13.0%) or chemotherapy alone (4.1%) were less common. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to a statistically significant annual percent change (APC) of 7.2% (95% CI 5.6-8.9). Increasing decade of age (risk ratio [RR] 1.15; 95% CI 1.09-1.23), increasing calendar year of diagnosis (RR 1.07; 95% CI 1.05-1.08) and stage IV disease (RR 2.66; 95% CI 2.3-3.07) were associated with a higher probability of receiving NACT. Other variables were not associated with receipt of NACT. Among patients who underwent cytoreductive surgery, the proportion who achieved no gross residual disease remained stable over the course of the study period in both complete case (APC 0.5%; 95% CI -1.8 to 0.9) and multiply imputed (APC -0.1%; 95% CI -1.6 to 1.3) analyses. Conclusions: The use of NACT for patients with LGSOC increased substantially from 2004 to 2020. Despite increased utilization of NACT, the rate of complete cytoreduction has not improved over the study period, possibly calling into question the effectiveness of NACT in reducing tumor burden in this setting.
Ovarian cancer and bevacizumab: Real-world use across western countries and effect on survival in high-risk subgroups.
Authors: Lindemann Kristina , Abreu Miguel , de Lurdes Batarda Maria , Boll Dorry , Ekmann-Gade Anne Weng , Hansen Jesper , Haug Ala Jabri , HÃ¸gdall Claus , Korach Jacob , Van Nieuwenhuysen Els , Ottevanger P. B. , Polterauer Stephan , Henrichsen Schnack Tine , Agesen Trude , Waldemarson Sofia , Andersen Klaus Kaae , Marth Christian 
Published: June 2023

5587 Background: Bevacizumab (bev) may be part of first-line treatment for patients with “high-risk” epithelial ovarian cancer (OC) (GOG-0218 and ICON7 trials). The prevalence of high-risk patient subgroups, including bev use and its effect on survival in a real-world setting is not well studied. Methods: The observational multi-country cohort study RESPONSE collected retrospectively medical record data on women with newly diagnosed advanced high-grade serous or endometrioid OC (DOI: 10.1002/cncr.34350). We analysed patients defined as ‘high-risk’ according to ICON7 definition as either 1) stage IV disease, 2) inoperable stage III disease or 3) sub-optimally debulked (>1 cm residual disease) stage III disease. Unadjusted Cox proportional hazards regression analysis was performed to estimate the association of bev with the risk of death. Follow up time was calculated from time between response assessment at the end of primary chemotherapy and death or 20 months follow-up, whichever occurred first. Results: Of 954 patients in total, we identified 386 high-risk patients (40%) treated with platinum-based chemotherapy. Of these, 132 (34%) received bev maintenance treatment. Baseline characteristics did not differ between patients receiving bev or no bev. Bev use was associated with a statistically significant reduction in risk of death with a HR of 0.49 (95%Ci: 0.18-0.78, p=0.002) in the total group of high-risk patients. The effect on survival was most evident among inoperable stage III/IV patients (n=151) with a 63% reduction in risk of death (HR 0.37; 95% CI (0.18-0.78, p=0.009). Risk estimates for additional subgroups are given in the table. Conclusions: Forty percent of this real-world population are considered high-risk according to ICON-7 and a majority of these patients did not receive bev during first-line treatment. In line with ICON 7, this analysis supports the beneficial effect of bev on overall survival in this high-risk population. Patients who do not receive surgery are underrepresented in clinical trials and this real-world study confirms the strong benefit of bev particularly in this subgroup. Any real-world study may be limited by the potential presence of selection bias of patients to receive bevacizumab or not. [Table: see text]
Predictors of long-term progression-free survival (PFS) in niraparib-treated patients (pts) from the PRIMA/ENGOT-OV26/GOG-3012 study.
Authors: Graybill Whitney , Pardo Beatriz , O'Malley David M. , Vergote Ignace , Monk Bradley J. , Auranen Annika , Copeland Larry J. , Sabbitini Roberto , Herzog Thomas J , Follana Philippe , Pothuri Bhavana , Braicu Elena Ioana , McCormick Colleen , Yubero-Esteban Alfonso , Moore Richard G. , Vuylsteke Peter , Raashouu-Jensen Nicoline , York Whitney , Hartman John , Gonzalez Martin Antonio 
Published: June 2023

5589 Background: Niraparib was approved as maintenance therapy for pts with advanced ovarian cancer (OC) after complete or partial response (CR/PR) to first-line (1L) platinum-based chemotherapy (CT) based on results from the PRIMA study. In this post hoc analysis, we identified factors associated with long-term PFS. Methods: PRIMA is a phase 3, randomized study of pts with newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer at high risk for relapse with CR/PR after 1L platinum-based CT. Pts were randomized 2:1 to niraparib 200 or 300 mg or placebo QD, and stratified by best response to 1L CT (CR/PR), neoadjuvant CT (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient or not determined [HRp/nd]). Investigator-assessed PFS was dichotomized in niraparib-treated pts with progressive disease (PD)/censoring <2 years vs PD/censoring ≥2 years after randomization (data cut, Nov 17, 2021). Logistic regression modeling using backward elimination (significance level=0.15) was used to identify baseline covariates associated with long-term PFS. Results: Of 487 niraparib-treated pts, 152 (31%) had PD/censoring ≥2 years after randomization. Odds ratios (OR) for PFS ≥2 years by baseline subgroup are shown (Table). The logistic regression model showed that BRCA mutation and HRD status, International Federation of Gynecology and Obstetrics (FIGO) stage, fallopian tube as the site of the primary tumor, and absence of baseline nontarget lesions were associated with longer PFS. Eastern Cooperative Oncology Group (ECOG) performance score, body mass index, age, time from CT to randomization, number of target lesions, best response after CT, number of CT cycles, type of debulking surgery, and residual disease were not associated with PFS ≥2 years. Safety has been reported previously ( Ann Oncol. 2022;33[suppl 7]:S789). Conclusions: Results suggest that long-term PFS in pts treated with niraparib may be associated with BRCA/HRd biomarker status, FIGO stage, primary tumor site, and number of baseline non-target lesions. These data are hypothesis generating. Clinical trial information: NCT02655016 . [Table: see text]
Utility of Ki67 in guiding adjuvant abemaciclib therapy for patients with hormone receptor (HR)-positive, early breast cancer (EBC).
Authors: Patel Rima , Bilani Nadeem , Tiersten Amy , Sparano Joseph A. 
Published: June 2023

559 Background: The monarchE trial found that the addition of adjuvant abemaciclib to endocrine therapy in pts with lymph node (LN)+, HR+ EBC improved invasive disease-free survival in two pt cohorts: (1) ≥ 4 +LNs or 1-3 +LNs and Grade 3 disease or tumor ≥ 5 centimeters and (2) 1-3 +LNs and Ki67 ≥ 20%. The FDA approved adjuvant abemaciclib only in pts with HR+, HER2-negative, LN+ EBC with Ki67 ≥ 20%. The role of Ki67 as a predictive biomarker in this setting is unclear. ASCO guidelines recommend offering abemaciclib to pts who meet eligibility for either cohort and not restricting inclusion by Ki67. The objectives of this study were to (1) determine the association between Ki67 and the 21-gene recurrence score (RS), an established prognostic and predictive biomarker, using Ki67 cutoff ≥ 20% and (2) compare eligibility for adjuvant abemaciclib by FDA versus ASCO criteria. Methods: Women with HR+, HER2-negative EBC with 1-3 +LNs, diagnosed between 2018 and 2019, and who had available information on Ki67 and RS in the National Cancer Database were identified. Pts were categorized into Ki67 low ( < 20%) or high ( ≥ 20%) based on cutoff used in the monarchE and stratified by RS of low-intermediate (0-25) or high (26-100). Stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. McNemar’s test was used to compare proportion of pts eligible for abemaciclib by FDA versus ASCO criteria. Results: 5,137 eligible women were included. 61.1% (n = 3,140) had Ki67 < 20% and 38.9% (n = 1,997) Ki67 ≥ 20%. There was fair agreement (Kappa 0.21-0.40) between Ki67 and RS, which was statistically significant (Kappa = 0.25, p < 0.001). Overall, using the FDA criteria for abemaciclib, 38.9% (n = 1,997) of patients would be eligible while based on ASCO criteria, 43.5% (n = 2,235) could be offered adjuvant abemaciclib (p < 0.001). Among the 2,235 patients eligible for abemaciclib based on ASCO criteria, 57.0% (n = 1,273) were eligible due to Ki67 ≥ 20% alone, 10.6% (n = 238) due to Grade 3 alone, while 32.3% (n = 724) satisfied both Ki67 ≥ 20% and Grade 3 criteria. There were 3,431 patients who were post-menopausal with RS 0-25 and would be spared chemotherapy, yet 35.3% (n = 1,212) would be eligible for adjuvant abemaciclib based on FDA or ASCO criteria. Conclusions: There was only fair agreement between Ki67 and RS in patients with 1-3 +LNs based on Ki67 cutoff of 20%. Among patients with LN+ EBC, more patients would be offered abemaciclib using ASCO criteria compared to FDA criteria. Most were eligible for abemaciclib based on Ki67 alone, suggesting that Ki67 may provide additional information beyond tumor grade. In postmenopausal women with 1-3 +LNs, about 30% may be spared adjuvant chemotherapy based on the RS but still be sufficiently high risk to be considered for adjuvant abemaciclib.
The effect of megestrol acetate ± pterostilbene in endometrial cancer: A prospective, randomized, window-of-opportunity clinical trial.
Authors: Senguttuvan Rosemary , Frankel Paul Henry , Ruel Nora , Kebria Mehdi , Han Ernest Soyoung , Song Mihae , De Leon Maria , Invernizzi Marta , Eng Melissa , Tinsley Raechelle , Li Aimin , Schmolze Daniel , Chang Sue , Arias Stella Javier , Dellinger Thanh Hue 
Published: June 2023

5597 Background: Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant found naturally at highest concentrations in blueberries. Its anti-tumor effects in preclinical studies of various solid tumors include carcinogenesis, inflammation, reactive oxygen species (ROS) formation, and antiproliferative effects. In endometrial cancer (EC), in vitro and in vivo studies demonstrated a synergistic antiproliferative effect of pterostilbene (PT) in combination with megestrol acetate (MA). No clinical trials testing the potential therapeutic benefit of pterostilbene in cancer have been completed. Methods: We performed a prospective, window-of-opportunity, randomized phase 2 clinical trial (NCT03671811) in patients with EC. Eligible patients had to be surgical candidates for treatment with hysterectomy and not have received prior therapy. The primary objective was to determine the effect of MA plus PT versus standard treatment of MA alone on tumor proliferation as measured by the Ki-67 index during the preoperative window. Patients were randomized 1:1 to one of two arms: MA+PT PO BID versus MA PO BID, for 3 weeks. The Ki-67 index was measured via hot-spot and H-score methodology in the preoperative tumor and hysterectomy specimen by two blinded pathologists whose measurements were averaged. The net change between pre- and post-operative specimens was calculated for each patient and expressed as a percentage. Toxicity was assessed using CTCAE grading. Results: A total of 44 patients with EC of all histologies were recruited to the study and included in the toxicity analysis. Median age was 61.9 years. Baseline demographics were comparable between both arms. Median treatment duration was 21 days (14-56), similar in both arms. One G3 hypertension was encountered in the MA arm; one G3 thromboembolic event in the MA+PT arm. Of 35 patients with sufficient treatment duration (>10 days) and available pre-and post-treatment specimens, 29 patients with endometrioid histology were evaluated for the ki67 analysis: 14 in the MA arm and 15 in the MA+PT arm. The MA+PT group demonstrated a -41.1% change in Ki-67 index by Hot Spot Score compared to -27.5% in the MA-only group (p=0.17). A similar trend was observed for the Ki-67 index by H Score methodology (-41.6% vs -26.7%, MA+PT vs MA, p=0.17). Conclusions: The combination of MA + PT in preoperative treatment of endometrial adenocarcinoma is well tolerated. The addition of Pterostilbene demonstrates a trend towards decreased Ki-67 index in endometrioid EC patients. Molecular studies are pending to delineate biomarkers associated with response. Clinical trial information: NCT03671811 .
Overall survival and subsequent therapy from a phase II study of sintilimab and anlotinib in patients with advanced or recurrent endometrial cancer.
Authors: Zeng Zhen , Wei Wei , Cui Lanyue , Jiang Zhihao , Li Jundong 
Published: June 2023

5598 Background: Although the combination of immunotherapy and antiangiogenic agents has been proved a promising strategy in endometrial cancer, studies in Chinese patients are limited. In the earlier phase II study (NCT04157491), Chinese patients with recurrent or advanced endometrial cancer treated with sintilimab + anlotinib had an objective response rate of 73.9% (95% confidence interval [CI]: 51.6% to 89.8%). Here we further updated overall survival (OS) and subsequent therapy for this study. Methods: Patients with endometrial carcinoma progressed after platinum-based chemotherapy were enrolled. Sintilimab 200 mg was supplied intravenously on day one, whereas anlotinib 12 mg was administered orally on day 1 - 14 every three weeks. Results: Twenty-three patients were enrolled in the study. 47.8% of patients received ≥ 2 lines of prior chemotherapy; microsatellite instability-high/mismatch repair deficiency (MSI-H/dMMR) and microsatellite instability stable/mismatch repair proficient (MSS/pMMR) accounted for 39.1% and 60.9% of patients, respectively. We observed a median OS of 17.8 months (95% CI, 9.4 to 26.3 months). Patients with microsatellite instability-high (MSI-H) had superior OS than their counterparts (not available vs. 13.3 months; HR 0.15, 95% CI, 0.33-0.70; P = 0.006). All patients had dropped out of the cohort [56.5% progression disease (PD), 13.0% adverse events (AE)]. Notably, five patients with partial responses (PRs) obtained pathological or radiography complete responses (CRs) in the follow-up. Pathological CRs were confirmed in three patients with long-lasting PRs who underwent surgery, consistent with PET/CT scans. Two patients with PR continued to have tumor shrinkage following treatment cessation due to AE and achieved CR during follow-up. Three out of four patients with CR experienced recurrences. There were no new grade 3-4 AEs associated with therapy. Conclusions: In terms of OS, combining sintilimab and anlotinib had promising therapeutic effects. Pathological CR was observed in patients with long-lasting PR, thus exploratory surgery may be required in selected patients. Clinical trial information: NCT04157491 . [Table: see text]
Correlation of cardiovascular disease with racial disparities in endometrial cancer outcomes.
Authors: Depke Mitchell , Summey Rebekah , Hopp Elizabeth 
Published: June 2023

5602 Background: Survival for Black women with endometrial cancer (EC) is shorter than that for non-Hispanic White (NHW) women, with a rate ratio for mortality of 1.98 per the American Cancer Society. Cardiovascular risk factors and disease are also more prevalent in Black women than NHW women. In women with breast cancer, Black patients received less optimal management of comorbidities and experienced increased cardiovascular disease (CVD)-related mortality as compared to White women. Similar to breast cancer, we hypothesize that CVD contributes to EC mortality disparities for Black women. Methods: In this retrospective cohort study, SEER and institutional data were utilized to investigate the contribution of CVD to outcomes for Black EC patients. The primary outcome was the contribution of cardiovascular mortality to the overall survival of Black patients. Secondary outcomes included identifying rates of new cardiovascular diagnoses, renal dysfunction, and adequacy of blood pressure control. The SEER cohort was defined using SEER*Stat 8.4.0.1. Uterine cancer patients were identified from the 2020 SEER Research Data. Survival by cause of death and proportion of deaths by cause of death were analyzed. Raw and adjusted hazard ratios for cardiovascular mortality were calculated. Next, institutional data was used to investigate survival, CVD diagnoses, renal dysfunction, and HTN in EC patients. Results: The SEER cohort contained 192,465 patients. Of these, 153,878 (80.8%) were White and 19,906 (10.3%) were Black. Black race was associated with decreased survival among patients who died of cardiovascular causes (HR 1.51, 95% CI 1.4 - 1.63, p < 2*10-16). When adjusted for age, stage, and histology, the hazard for decreased survival remained elevated for Black patients who died of cardiovascular causes (adjusted HR 1.65, 95% CI 1.52-1.77, p < 2*10-16). Our institutional cohort included 1491 patients, 1263 (84.7%) White and 151 (10.0%) Black. Black patients had a relative risk of death of 1.92 (95% CI 1.38 - 2.61) compared with White patients. Among patients with CVD, the hazard for death was 2.02 (95% CI 1.39 - 2.80). Black patients had significantly higher blood pressure, creatinine, and eGFR measurements. Conclusions: Racial outcome disparities in EC are multifactorial. CVD management will become increasingly important with the use of targeted therapies including lenvatinib and trastuzumab. Our study highlights an additional area of disparity and suggests possible interventions.