bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to subsequent platinum-based chemotherapy post PARP inhibitor in recurrent epithelial ovarian cancer.
Authors: MacAulay Vacheresse Genevieve , Sabri Elham , Domingo Sheryl , Le Tien 
Published: June 2023

5578 Background: Maintenance therapy with PARP inhibitors (PARPi) can increase progression free survival (PFS) for recurrent or metastatic platinum-sensitive epithelial ovarian cancer (EOC). Little is known about disease trajectory following treatment with these agents, though some evidence suggests a decreased response to subsequent platinum-based chemotherapy. This retrospective cohort study assessed real-world response rates to platinum-based chemotherapy for recurrent high grade EOC following treatment with a PARPi. Methods: All patients prescribed a PARPi as maintenance therapy for recurrent or metastatic EOC at the Ottawa Regional Cancer Center (ORCC) from September 2017 to May 2022 were included. PFS following penultimate therapy (line of therapy preceding PARPi initiation) as well as the PFS following subsequent platinum-based chemotherapy in patients with disease progression more than 6 months after penultimate therapy were calculated. Incidence of platinum resistance in patients with disease progression following PARPi therapy was determined. Results: 91 patients were included in the analysis including 54 patients on niraparib and 36 patients on olaparib. Follow-up after initiation of PARPi ranged from 4.6 months to 62.0 months with a median of 16.3 months. 54 (59.3%) of patients experienced disease progression after initiation of PARPi therapy, including 10 (11.0%) who progressed within 6 months of their penultimate therapy. Of the 44 patients who experienced disease progression more than 6 months following penultimate therapy, 32 (72.7%) were rechallenged with platinum-based chemotherapy. Of these, 16 (50.0%) experienced further disease progression with 14 (43.8%) progressing within 6 months of their platinum rechallenge. Median PFS following platinum rechallenge was 4.4 months (from 0.8 months to 34.9 months), significantly lower than previous reports. Conclusions: Patients who experienced disease progression following PARPi therapy showed a poor response to subsequent platinum-based chemotherapy, even when progression occurred more than 6 months after completion of their penultimate platinum-based chemotherapy. This supports the theory that PARPi resistance may be a surrogate for platinum resistance and raises concern for possible contribution of PARPi in the induction of platinum resistance in recurrent EOC.
Molecular and immune profiling of TP53-mutated ovarian cancers with non-BRCA1/2 homologous recombination gene alterations.
Authors: Strickland Kyle C. , Previs Rebecca A. , Wallen Zachary D , Nesline Mary K , Ko Heidi Chwan , Pabla Sarabjot , Hastings Stephanie , Jensen Taylor J. , Reddy Prasanth , Severson Eric A , Ramkissoon Shakti 
Published: June 2023

5579 Background: Molecular alterations in homologous recombination (HR) pathway genes lead to HR deficiency (HRD) in ~50% of high grade serous ovarian carcinomas (HGSOC). The immune microenvironment of BRCA1/2-mutated HGSOC has been extensively characterized, in contrast to tumors with mutations in other HR genes. We evaluated a cohort of epithelial ovarian cancers (EOC) enriched for HGSOC and compared molecular and immune signatures of tumors with BRCA1/2 mutations ( BRCAm) to those with non-BRCA1/2 HR gene mutations (NBHRD). Methods: We characterized 173 EOC by comprehensive genomic and immune profiling (CGIP) using panel-based next-generation DNA (523 genes) and RNA sequencing (384 genes), respectively. We enriched for HGSOC by selecting for TP53 mutations and excluding tumors with non-serous histology or any mutation in POLE, MLH1, PMS2, MSH2, MSH6, or nucleotide excision repair genes. Tumors lacking BRCA1/2-mutations were classified as NBHRD if a reportable mutation was present in canonical HR genes. Mutational burden (TMB, mut/Mb) was estimated from detected SNV/indels. We calculated immune-related expression signatures, including tumor immunogenicity score (TIGS), cellular proliferation (CP), and cancer testis antigen burden (CTAB). PD-L1 expression was assessed by tumor proportion score (TPS) following 22C3 immunohistochemistry. Differences in TMB, TIGS, CP, CTAB, PD-L1 and gene expression rank were tested for using Wilcoxon rank-sum test. Results: Of 173 EOC, 84 cases had complete CGIP, including 11 (13%) BRCAm, 7 (8%) NBHRD (Table), and 66 (79%) lacking HR gene alterations. On average, NBHRD tumors harbored lower TMB (4.1±2.3 vs. 6.6±2.3 vs. p=0.03) and elevated TIGS (59.1±16.2 vs. 41.7±16.2 p=0.044) compared to BRCAm tumors. We found no difference in PD-L1 (p=0.21), CP (p=0.26), or CTAB (p=0.48). Expression changes were identified in 32 immune genes, of which 31 (97%) were substantially up-regulated (1.3-3.3 fold) in NBHRD compared to BRCAm tumors. Conclusions: Our findings showed our cohort of NBHRD tumors were more immunogenic but less mutagenic than BRCAm tumors, implying enhanced immunogenicity unrelated to neoantigen load. Given that immune checkpoint inhibitors have shown limited efficacy in ovarian cancer, our data suggest NBHRD tumors may have stronger and possibly distinct immune escape mechanisms compared to BRCAm tumors. [Table: see text]
Exploring the significance of PARP inhibitor therapy after first-line chemotherapy in patients with homologous recombination proficient ovarian cancer: An extracted individual patient data and trial-level meta-analysis.
Authors: Cunha Mateus Trinconi , Lazar Neto Felippe , Estevez-Diz Maria Del Pilar , Bonadio Renata Colombo 
Published: June 2023

5580 Background: The use of poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy in advanced epithelial ovarian cancer (EOC) patients (pts) has shown to delay cancer progression among patients with mutated BRCA (mBRCA) or homologous recombination deficiency (HRD), with debatable and divergent benefit among the subgroup of patients with homologous recombination proficiency (HRP). We aimed to further clarify the efficacy of PARPi after first-line chemotherapy (1L CT) in patients with HRP EOC. Methods: A systematic literature search of PubMed, Embase, The Cochrane Library until February 9th was conducted to identify articles or presentations of phase III clinical trials (P3CT) evaluating PARPi maintenance therapy after 1L CT in ovarian cancer. Individual patient data was reconstructed from Kaplan-Meier plots of progression-free survival (PFS) among pts with mBRCA, HRD and HRP through WebPlotDigitizer and R package IPDfromKM and futher combined. We also performed trial-level meta-analysis with a random effects model. Comparisons were made with Cox proportional hazards. Clinical benefit for each sub-group was accessed with the ESMO Magnitude of Clinical Benefit Formulary 2b (ESMO MBCS). Results: The literature search resulted in 513 items. After screening, 6 P3CT (SOLO1, PRIMA, VELIA, PAOLA, PRIME, and ATHENA-MONO) were selected, and the longer follow-up data of each trial was used. A total of 3205 pts were included in the analysis (2090 in PARPi arms, 1115 in control arms). HRP was associated with worse PFS regardless of the treatment arm (HRP vs mBRCA in PARPi arms: HR 1.92, 95% CI 1.62 – 2.21, P < 0.001). Compared to control treatment arm, PARPi therapy was associated with a improved PFS in all subgroups, although the magnitude of benefit decreased from mBRCA to HRD and HRP (Table). Trial-level meta-analysis yielded similar results. PARPi therapy summed 4 out of 4 possible points at ESMO MBCS for mBRCA and HRD, but only 2 points among HRP pts, confirming a lower clinical benefit in this subgroup. Conclusions: This meta-analysis included additional P3CT recently presented and new data of subgroup analysis of previous studies. Results confirm a statistically significant benefit of PARPi maintenance after 1L CT for HRP EOC. Nevertheless, the relative and absolute gain in PFS is modest (9% in 2 years), while mBRCA and HRD subgroups have a substantial benefit. The worse prognosis of HRP pts, in addition to the small clinical benefit of PARPi therapy, highlights the need for new treatment strategies for this subgroup. [Table: see text]
Healthcare access dimensions and uterine cancer survival: A National Cancer Database study.
Authors: Anastasio Mary Katherine , Gupta Anjali , Akinyemiju Tomi F. , Previs Rebecca A. 
Published: June 2023

5594 Background: Racial disparities persist throughout the continuum of care for Black patients with uterine cancer. Few studies have evaluated how multiple dimensions of healthcare access (HCA) contribute to these disparities in patients who present at an advanced stage and meet criteria for adjuvant therapy. Methods: Patients with Stage III-IV uterine cancer between 2004-2015 who received adjuvant therapy with complete sociodemographic and other relevant covariate data were identified in the National Cancer Database (NCDB). Race and ethnicity were defined as non-Hispanic (NH)-Black, Hispanic, and NH-White. Healthcare access dimensions of affordability, availability and accessibility were measured using variables defined in the NCDB. Overall survival was analyzed using Kaplan-Meier curves, log-rank test, and multivariable Cox proportional hazard models. Results: The study cohort included 43,134 patients: 78.8% NH-White, 15.3% NH-Black, and 5.9% Hispanic. Compared to NH-White and Hispanic patients, NH-Black patients were more likely to have Type II (75.6% vs. 53.9% and 55.4%) and Stage IV disease (40.8% vs. 30.7% and 32.3%). NH-Black patients were more likely to receive chemotherapy alone (53.5% vs. 43.1% and 46.2%) compared to NH-White and Hispanic patients. NH-Black patients were the most likely to have government funded insurance (58.6% vs. 50.3% and 50.4%) and live in the lowest income quartile (46.4% vs. 14.2% and 29.9%) compared to NH-White and Hispanic patients. NH-Black patients had a significantly higher risk of death than NH-White patients when adjusting for demographic/clinical characteristics and all three healthcare access dimensions (HR 1.29; 95% CI 1.24, 1.34). Conclusions: Healthcare access affordability predicts survival but does not fully explain racial disparities in survival rates of patients with advanced stage uterine cancer. NH-Black patients are more likely to have aggressive disease, receive chemotherapy alone, and have worse survival than NH-White patients regardless of pathogenic subtype. Investigating additional healthcare access dimensions may be critical to addressing disparities in uterine cancer.
Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.
Authors: Santin Alessandro , McNamara Blair , Siegel Eric R. , Harold Justin , Mutlu Levent , Altwerger Gary , Huang Gloria S. , Andikyan Vaagn , Clark Mitchell B. , Ratner Elena , Azodi Masoud , Dottino Peter , Schwartz Peter E. , Bellone Stefania 
Published: June 2023

5599 Background: Despite recent advances, there remains a significant need for targeted, efficacious treatments for advanced and recurrent endometrial carcinoma (EC). Trop-2 has been demonstrated to be overexpressed in several EC including grade 3 endometrioid adenocarcinoma (96%), and uterine serous carcinoma (65%). Trop-2 overexpression has been found to confer a worse prognosis and predicts disease recurrence. Sacituzumab govitecan-hziy (SG) is an antibody-drug conjugate comprised of a humanized anti-Trop-2 antibody conjugated with the active metabolite of irinotecan, a topoisomerase-I inhibitor. SG is currently FDA-approved for use in metastatic urothelial cancer and metastatic triple-negative breast cancer. Methods: We report results from the stage 1 of an open-label non-randomized phase 2 trial (NCT04251416) established to evaluate the clinical activity of SG in patients with persistent or recurrent EC of epithelial origin with Trop-2 overexpression. Criteria for study participation included radiographically confirmed and measurable persistent or recurrent EC, progression after or during platinum-based chemotherapy, and at least 2+ staining of Trop-2. One target lesion by RECIST v1.1 and adequate bone marrow, renal, and hepatic function were required. Patients were at least two weeks beyond prior treatment, major surgery, or high dose systemic corticosteroid use. Patients were given 10mg/kg of SG administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles. This 3-week cycle was continued without rest until disease progression or unacceptable toxicity. Results: Twenty-one patients were enrolled into stage 1. Ten patients (48%) had uterine serous carcinoma, seven (33%) had endometrioid adenocarcinoma, three (14%) had carcinosarcoma, and one patient had mixed serous and clear cell histology. All patients received at least one prior line of chemotherapy, (median 3 lines, range 1-6). At the time of submission, 20 patients were response-evaluable (Table); seven (35%) achieved objective response (5 out of 7 confirmed). Eighteen patients were evaluable for durable disease control; 7 (39%) achieved it. Follow-up durations had a median (IQR) of 15.6 (5.7–22.5) months. Median OS was 22.5 months, and median PFS was 5.7 months. The treatment was well-tolerated with no new or unexpected safety signals reported. Conclusions: Sacituzumab govitecan shows remarkable clinical activity against some of the most historically challenging and chemotherapy-resistant endometrial pathologies and demonstrates a favorable safety profile. With these promising results, we will begin the stage 2 expansion of this phase 2 trial. Clinical trial information: NCT04251416 . [Table: see text]
Influence of ovarian function supression on quality of life in breast cancer survivors during adjuvant endocrine therapy.
Authors: Dedic Plavetic Natalija , Dugonjic Okrosa Ana , Silovski Tajana , Jovic Zlatovic Josipa , Jajac Brucic Lana , Skelin Marko , Mucalo Iva 
Published: June 2023

560 Background: Adding ovarian function suppression to adjuvant endocrine therapy (AET) lowers the disease recurrence rates among premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). However, a detrimental effect on endocrine symptoms burden (ESB) is expected. Therefore, this study aimed to investigate differences in Quality of life (QoL) and endocrine symptoms in premenopausal women prescribed AET, with/without gonadotropin-releasing hormone agonist (GnRH). Methods: This cross-sectional study included women, with HR+ EBC, premenopausal at diagnosis, treated with AET for more than 3 months, with and without GnRH. The research was conducted with institutional Ethics Committee approval at the University Hospital Centre Zagreb, General Hospital Šibenik, and with online survey. A validated instrument, the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES), was used. The collected data were analysed using SPSS v. 29 (p≤0.05). Results: Overall, 314 eligible BC survivors with a median age of 45 years (22-65) and a median duration of AET of 2 years (3 months -12 years) responded to FACT-ES and were included in the analysis. Altogether 45.2% (n=142) of participants were prescribed tamoxifen (TAM), 25.8% (n=81) GnRH+TAM, and 29% (n=91) GnRH+aromatase inhibitor (AI); exemestane (9%), letrozole (13.6%) and anastrozole (6.4%). The total QoL (FACT-ES) score was higher in patients treated with TAM as opposed to patients treated with AI+GnRH (p=0.01). Adding GnRH to TAM did not significantly change QoL when compared to TAM alone or AI+GnRH. In addition, patients on AI+GnRH had lower physical well-being (PWB) score than patients on TAM+GnRH (p=0.03) or TAM alone (p=0.05) and lower endocrine subscale score (ESS-19) than patients on TAM (p=0.01), indicating more endocrine symptoms in premenopausal women treated with AI+GnRH. Among patients treated with AI+GnRH letrozole had lower PWB (p=0.03) and ESS-19 score (p=0.01) than exemestane. Conclusions: This study showed that GnRH+AI in premenopausal women with HR+ EBC results in greater ESB and lower QoL compared to patients treated with TAM or GnRH+TAM. Therefore, interventions helping decrease the ESB in patients treated with AI+GnRH should be explored and developed to help patients adhere to and persist in AET. [Table: see text]
Racial and ethnic disparities in quality of diagnostic evaluation for uterine cancer among Medicare patients.
Authors: Xu Xiao , Chen Ling , Wright Jason Dennis 
Published: June 2023

5600 Background: Uterine cancer is the most common gynecologic malignancy. As there is no routine screening for uterine cancer, appropriate evaluation of presenting symptoms is crucial for early diagnosis. We examined racial/ethnic disparities in the quality of diagnostic evaluation received by Medicare patients with uterine cancer. Methods: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified patients ≥65 years with uterine cancer diagnosed in 2008-2017 who presented with abnormal uterine bleeding (AUB, the most common symptom of uterine cancer). Patients with other cancer or unknown race/ethnicity were excluded. Race/ethnicity was categorized as White, Black, Hispanic, or Other (including American Indian/Alaska Native and Asian/Pacific Islander). Quality of diagnostic evaluation was measured by: 1) not receiving guideline-recommended diagnostic procedures (yes/no), and 2) number of days between AUB presentation and first diagnostic procedure. We compared these measures across racial/ethnic groups using multivariable regressions adjusting for patient sociodemographic characteristics, comorbid conditions, histology, and tumor grade. We further examined racial/ethnic differences in stage at diagnosis before vs. after accounting for these quality indicators. Results: The sample included 23,017 patients. Compared to White patients, Black, Hispanic, and Other patients were younger; more likely to reside in a metropolitan area, lack preventive care in the past year, or have comorbidities; and tended to have uterine cancer of non-endometrioid types and higher grade (p<0.001 for all). A larger proportion of Black than White patients did not receive guideline-recommended diagnostic procedures (Black: 9.6% vs. White: 5.0%, p<0.001; adjusted odds ratio [aOR] = 1.45, 95% CI: 1.20-1.74). Time from AUB presentation to first diagnostic procedure was longer for Black than White patients (90th percentile: 34 vs. 21 days, p<0.001; adjusted mean ratio = 1.38, 95% CI: 1.21-1.57). Black patients were more likely than White patients to be diagnosed at regional (aOR = 1.18, 95% CI: 1.04-1.33) or distant stage (aOR = 1.27, 95% CI: 1.06-1.52), rather than localized stage, even after adjusting for other characteristics. Further adjusting for quality of diagnostic evaluation slightly reduced Black-White differences in stage at diagnosis (regional: aOR = 1.16, 95% CI: 1.03-1.32; distant: aOR = 1.23, 95% CI: 1.03-1.48). Hispanic and Other patients also experienced delay in time to first diagnostic procedure, but they did not differ from White patients in receipt of guideline-recommended diagnostic procedures or stage at diagnosis. Conclusions: There were racial/ethnic disparities in the quality of diagnostic evaluation received by Medicare patients with uterine cancer, which may partially explain Black-White differences in their stage at diagnosis.
Efficacy and safety of anlotinib in overall and disease-specific advanced gynecological cancer: A real-world study.
Authors: Hong Xinyi , Qiu Shanhu , Wu Xia , Chen Sizhen , Chen Xiaoxiang , Zhang Bei , He Aiqin , Zhou Ying , Xu Yun , Wang Jianqing , Gao Yingchun , Xu Xizhong , Sun Li , Zhang Yang , Xiang Libing , Zhou Jundong , Guan Qun , Chen Bingwei , Shen Yang 
Published: June 2023

5608 Background: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer. We conducted this study to address this issue in the real-world setting. Methods: Data from patients treated with anlotinib for persistent, recurrent or metastatic gynecological cancer including cervical, endometrial, and ovarian cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1–14 every 3 weeks until disease progression, severe toxicity occurred, or death. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.46 months. The overall ORR and DCR were 28.1% (95% CI 22.6% to 34.1%), and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to anlotinib use was pain/arthralgia (18.3%). Conclusions: In conclusion, anlotinib holds promise in treating patients with advanced gynecological cancer, such as cervical, endometrial, and ovarian cancer, with reasonable efficacy and tolerable safety.
Do HER2 low tumors have a distinct clinicopathologic phenotype?
Authors: Polidorio Natália , Veeravalli Srinivasa Sevilimedu , Montagna Giacomo , Le Tiana , Morrow Monica 
Published: June 2023

570 Background: Clinicopathologic features of breast cancer subtypes defined by hormone receptor (HR) and HER2 status differ. These analyses classified HER2 IHC <3+ with negative FISH as HER2-. With the recognition of the clinical relevance of HER2 low, there is debate as to whether this is a distinct subtype. We sought to determine if features of HER2 low tumors differ from HER2- and HER2+ after controlling for HR status. Methods: Patients undergoing upfront surgery from 1998 to 2010 were identified from a prospectively maintained institutional database. HER2 status was classified by IHC/FISH analysis as HER2-, HER2 low (IHC 1+ or 2+ with negative FISH), and HER2+ (IHC 3+ or FISH +) and stratified by HR status. Univariable (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Results: 11,323 tumors from 11,072 patients were included. 5,104 (45%) were HER2 low, 41.2% were HER2- and 13.6% were HER2+. On MVA stratified by HER2 status only, compared to HER2- tumors, HER2 low was associated with LVI (OR 1.2 [95% CI 1.06-1.36]; p=.003), multifocality (OR 1.26 [95% CI, 1.12-1.42]; p<.001), nodal micrometastasis (OR 1.15 [95% CI, 1.02-1.31]; p=.024), and lower rates of <3 positive nodes (OR 0.77 [95% CI, 0.66-0.90], p=.001). HER2+ was associated with younger age, high grade, multifocality, extensive intraductal component (EIC), and pN2/3 nodal stage. Clinicopathologic features stratified by HR and HER2 status are shown in the table. On UVA, in both HR+ and HR– tumors, age and multifocality were associated with HER2 low, and LVI, multifocality, and EIC with HER2+ compared to HER2- tumors. On MVA, no variables were independently associated with both HR+ and HR-/HER2 low tumors compared to HER2-. In contrast, HER2+ tumors regardless of HR status were significantly associated with multifocality and EIC. Conclusions: HER2 low breast cancer features seem to be driven by HR status and HER2 overexpression. We do not have enough evidence to support the interpretation of HER2 low as a distinct subtype. [Table: see text]