bluuebunny/crossref_metadata_2025_split huggingface dataset:
State-of-the-art management of HER2-negative early breast cancer: Treatment patterns among healthcare professionals and concordance with expert recommendations.
Authors: Becker Marie N. , Abraham Jame , Kalinsky Kevin , Spring Laura , Traina Tiffany A. , Quill Timothy A. , Yardley Denise A. 
Published: June 2023

553 Background: The management of high-risk HER2-negative early-stage breast cancer (EBC) has recently evolved with the addition of newer agents including abemaciclib, olaparib, and pembrolizumab as (neo)adjuvant therapy options for appropriate patients. To aid healthcare professionals (HCPs) in the recommended implementation of these agents, we developed an online treatment decision support tool providing case-specific treatment guidance from 5 breast cancer experts. Here, we report an analysis of cases entered into the tool by HCPs, comparing their planned treatment with expert recommendations. Methods: Expert therapy recommendations for 10 case scenarios in high-risk HER2-negative EBC based on 3 pivotal clinical trials (KEYNOTE-522, OlympiA, and monarchE) were obtained in March 2022. Patient and disease characteristics included hormone receptor (HR) status, BRCA mutational status, lymph node positivity, presence of residual disease after resection, and additional criteria based on the 3 practice-changing trials. HCPs entered specific patient and disease factors into the tool along with their intended treatment plan and were shown 5 individual expert treatment recommendations for the unique case scenario. Results: From June 2022 to January 2023, 547 HCPs entered 982 patient case scenarios into the tool. A comparison of treatment recommendations by experts and HCPs showed divergence for several case scenarios. For patients with high-risk HR-positive/HER2-negative EBC and no BRCA mutation, all 5 experts recommended adjuvant abemaciclib plus endocrine therapy. By contrast, 64% of HCPs’ therapy choices were discordant with the experts, with 49% choosing chemotherapy followed by endocrine therapy. For patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy and have no residual disease, all 5 experts recommended observation, whereas 36% of HCPs recommended additional adjuvant therapy. In the setting of BRCA-mutated TNBC with residual disease after neoadjuvant pembrolizumab plus chemotherapy, 4 of 5 experts recommended adjuvant pembrolizumab plus olaparib, but just 33% of HCPs chose this combination. One third of HCPs who initially selected treatment options that diverged from expert recommendations or who were uncertain about treatment choice intend to change their therapy selection to align with the experts. Conclusions: Analysis of data from this tool suggests differences in clinical practice between experts and HCPs for multiple case scenarios of high-risk EBC, including examples of potential overtreatment. Moreover, our data demonstrate that this decision support tool may lead to better alignment of HCP treatment choices with experts, with the potential to improve clinical management of patients.
Patient-reported outcomes during pelvic radiation therapy: A secondary analysis on sexual function from NRG-RTOG 1203.
Authors: Corrigan Kelsey L , Paulus Rebecca , Klopp Ann , Wenzel Lari B. , Yeung Anamaria R , Thompson J Spencer , Doncals Desiree E. , Kundapur Vijayananda , Wiggers Nancy H , Mohan Dasarahally S. , Ghamande Sharad A. , Westin Shannon Neville , Schnarr Kara , Haas Michael , Gaffney David K. , Waggoner Steven E. , Vanderwall Pamela , Jastaniyah Noha , Pugh Stephanie L. , Kachnic Lisa A. 
Published: June 2023

5533 Background: NRG-RTOG 1203 reported that intensity-modulated radiation therapy (IMRT) reduced patient-reported GI and GU toxicities in cervical/endometrial cancer patients receiving adjuvant RT, as compared to standard whole field pelvic RT (WPRT). We conducted a secondary analysis of patient-reported sexual function (PR-SF) to compare this endpoint among treatment groups and identify factors associated with sexual dysfunction. Methods: Patients on NRG-RTOG 1203 were randomly assigned to WPRT vs. IMRT and completed the PRO-CTCAE for GI toxicity and the cervical cancer FACT-Cx at baseline, week 5 of RT, and at 4-6 weeks, 1-year, and 3-years post-RT. Patient responses to FACT-Cx sexual function questions were analyzed. The between arm frequency and severity of responses were tested using chi-square. PR-SF was compared with PRO-CTCAE GI toxicity using chi-square. A repeated measures logistic regression model was used to determine the impact of clinical/treatment factors on sexual function by dichotomizing the responses. Results: Of the 279 patients included for primary analysis, 236 (85%) completed PR-SF questions; 125 (53%) in the WPRT arm and 111 (47%) IMRT. There were no significant differences in PR-SF between treatment groups (p>0.05). PR-SF improved for both groups post-RT, except responses to “my vagina feels too narrow or short” worsened (Table). Women without abdominal pain interference at 4-6 weeks post-RT were less likely to fear sex (74.2% vs. 25.8%, P=0.03) and more likely to like their body appearance at 1 year (95.7% vs. 4.3%, P<0.01) compared to women with interference. Women liked the appearance of their body less during RT vs. at baseline (OR 1.95, 95% CI 1.04-3.64, P=0.04). Women were less interested in sex during RT in both arms (WPRT: OR 3.61, 95% CI 1.40-9.34; IMRT: OR 3.96, 95% CI 1.02-15.34) and at 4-6 weeks post-RT for IMRT (OR 3.16, 95% CI 1.14-8.72) vs. at baseline. Conclusions: PR-SF was similar between treatment groups. PR-SF during and post-RT was not significantly reduced compared to baseline with the exception of patients with abdominal pain interference, who had significantly worse PR-SF at 4-6 weeks and 1-year post-RT. Clinical trial information: NCT01672892 . [Table: see text]
Final results of a phase II trial of prolgolimab with platinum-based therapy and bevacizumab in patients with advanced cervical cancer.
Authors: Fogt Sergey , Andabekov Timur , Shamsutdinova Yana , Dvorkin Mikhail , Artamonova Elena , Chistyakov Valerii , Zukov Ruslan , Moiseenko Vladimir , Nechaeva Marina , Odintsova Svetlana , Fadeeva Natalia , Kislov Nikolai , Tantsyrev Denis , Tjulandin Sergei , Fomin Eugeniy , Linkova Iuliia , Zinkina-Orikhan Arina , Shustova Mariia , Zhukova Lyudmila 
Published: June 2023

5536 Background: Here we present the final results of single-arm phase II CAESURA (NCT03912402) study of prolgolimab (anti-PD-1 antibody) with platinum doublet and bevacizumab in subjects with advanced cervical cancer (CC). Methods: 58 patients (pts) with metastatic or recurrent/persistent CC with measurable disease received prolgolimab (3 mg/kg) Q3W together with paclitaxel, platinum drug (cis- or carboplatin) and bevacizumab for 6 cycles and then therapy with prolgolimab and bevacizumab until disease progression or toxicity. Objective response rate (ORR) was assessed by central radiology review per RECIST 1.1 (primary endpoint) and iRECIST criteria. CT scans were performed after 9 and 18 weeks of treatment and in case of suspicion on disease progression. Results: Distant metastases at screening had 42 pts, 16 had recurrent or persistent CC. The median age of pts was 48 [38; 58] years old. Squamous cell carcinoma was diagnosed in 50 of 58 subjects. PD-L1 CPS ≥ 1 (22C3) was found in 45 pts, CPS < 1 in 6 cases. ORR per RECIST 1.1 was 63.8% (37 of 58 pts) and included 2 complete, 35 partial responses. ORR per iRECIST was 70.7% (41 of 58 pts) with 2 complete and 39 partial responses. At the cut-off date (12 months) PFS (secondary endpoint) per RECIST 1.1 criteria counted 8.5 (95% CI 5.7; 10.9) months, per iRECIST criteria it reached 13.1 (95% CI 8.1; 13.6) months. Median overall survival was not reached. Any grade adverse events (AEs) occurred in 98% (57/58) of pts, of them in 69% (40/58) they were related to study treatment, including 12 cases of severe events (gr. 3 or higher). Immune-related AEs (irAEs) occurred in 38% (22/58) of pts. The most common irAEs were gr. 1–2 endocrine disorders (26%), including thyroid disorders and one case of gr. 2 adrenal insufficiency. Other important irAEs included 2 cases of enterocolitis (gr. 3 and 4), 1 case of dermatitis (gr. 3), several cases of gr. 2–3 transaminase elevation (9%). In 15 pts at least one component of study treatment was discontinued due to AE, of them 4 events were related to study treatment (including immune-related enterocolitis and adrenal insufficiency). Conclusions: Prolgolimab in combination with chemotherapy and bevacizumab demonstrated promising efficacy, known and acceptable safety profile in pts with advanced CC. Phase III placebo-controlled trial evaluating prolgolimab with chemotherapy and bevacizumab (NCT03912415) as first-line therapy option in subjects with CC is ongoing. Clinical trial information: NCT03912402 .
Association between serum folate and vitamin B12 and cervical high-risk human papillomavirus (HPV) infection.
Authors: Peitz Josephine , Adebamowo Clement Adebayo , Adebamowo Sally Nneoma 
Published: June 2023

5541 Background: Serum concentration of folate (vitamin B9) and vitamin B12 were inversely associated with cervical intraepithelial neoplasia and cervical cancer in some studies. The association between folate and vitamin B12, and human papillomavirus (HPV) infection has not been well elucidated. We evaluated whether low serum level of folate and vitamin B12 was associated with high-risk HPV (hrHPV) infection. Methods: The study population was 6,452 women, aged 18-59 years old, enrolled in the National Health and Nutrition Examination Survey (NHANES), from 2003 to 2016, in the United States. In this cross-sectional study, odds ratios (ORs) of hrHPV were calculated, by quintiles of low folate and vitamin B12 combined, using logistic regression models. Results: The mean age (standard deviation) of the women was 36.98 (12.19) years. Women in the lowest quintile had less than 20.6 nmol/L of folate and less than 248 pmol/L of vitamin B12. Some of the women, 23% (1,509/6,452), were hrHPV positive. In age-adjusted models, low folate and vitamin B12 was significantly associated with hrHPV infection. The ORs and 95% confidence intervals (CI) was (OR: 0.704, 95% CI: 0.509 - 0.975, p = 0.034) for the second, (OR: 0.671, 95% CI: 0.479 - 0.940, p = 0.020) third, (OR: 0.534, 95% CI: 0.370 - 0.770, p = 0.0008) fourth and (OR: 0.476, 95% CI: 0.33 - 0.679, p < 0.0001) fifth quintiles, compared to women in the lowest quintile. The association remained statistically significant after the models were further adjusted for smoking status and income level; women in the highest quintile were less likely to have hrHPV infection compared to those in the lowest quintile (OR: 0.541, 95% CI: 0.343 - 0.855, p = 0.008). Conclusions: This study supports an association between low serum levels of folate and vitamin B12, and hrHPV infection, among women in the United States.
The spectrum of homologous recombination deficiency in cervical cancer: Is it also a cervical issue?
Authors: Ahsan Muhammad Danyal , Webster Emily M. , Kahn Ryan M , Levi Sarah R. , Qazi Murtaza , Perez Luiza , Brewer Jesse T. , Keenahan Laura , Cantillo Evelyn , Chapman-Davis Eloise , Holcomb Kevin , Frey Melissa Kristen 
Published: June 2023

5543 Background: Tumors deficient in homologous recombination DNA damage repair (HR-DDR) demonstrate sensitivity to therapeutic agents targeting the HR-DDR pathway, such as poly-ADP ribose phosphate (PARP) inhibitors. The landscape of homologous recombination deficiency (HRD) is not well-characterized for cervical cancer; thus, we sought to analyze the prevalence of somatic pathogenic gene variants (PGVs) in HRD genes in cervical cancers. Methods: The American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 was queried for all cervical cancer tumors via cBioPortal (http://genie.cbioportal.org). This is a publicly available, multi-institutional database of next-generation sequencing (NGS) genomic profiles of multiple tumors. PGV frequencies of 27 genes involved in HR-DDR were descriptively reported for cervical cancer tumors, with histologic stratification: ATM, ARID1A, ATRX, BRCA1, BRCA2, BARD1, BRIP1, BLM, BAP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Results: A total of 857 cervical tumors from 817 patients were included for analysis. At least one somatic PGV in an HRD gene was found in 16.5% of all tumors (141/857). When stratified by histological subtypes with at least 25 tumors sequenced, highest frequencies of ≥1 PGV in HRD genes were observed in mucinous cervical cancer (13/66, 19.7%), cervical adenocarcinoma (48/262, 18.3%), squamous cell cervical cancer (53/349, 15.2%), adenosquamous cervical cancer (6/43, 14.0%) and neuroendocrine cervical cancers (5/42, 11.9%). Substantial rates of PGVs in HRD genes were also observed in histological subtypes with fewer than 25 sequenced tumors. Across all tumors, HRD genes with the highest frequencies of PGVs were ARID1A (9%), BAP1 (3%), ATM (1.6%) and BRCA1 (1.6%). Conclusions: NGS data demonstrate a substantial rate of somatic PGVs in HRD genes in cervical cancers, including among HPV related subtypes. These data suggest the need to expand routine functional HRD status assessment to cervical cancers in order to further characterize the landscape of HRD in these tumors. Furthermore, genetically driven clinical trials are warranted to evaluate the efficacy of HRD-targeted therapies such as PARP inhibitors, ataxia telangiectasia, and Rad-3 related kinase (ATR) inhibitors. [Table: see text]
Efficacy of subsequent therapies in patients (pts) with advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial according to whether disease progression occurred during or after the end of olaparib (ola) maintenance.
Authors: Harter Philipp , Mouret-Reynier Marie-Ange , Lorusso Domenica , Cropet Claire , Guerra Eva M. , Wolfrum-Ristau Pia , Matsumoto Takashi , Vergote Ignace , Colombo Nicoletta , Maenpaa Johanna Unelma , Lebreton Coriolan , de Gregorio Nikolaus , Mosconi Anna Maria , Rubio-Pérez Maria Jesús , Bourgeois Hugues , Fasching Peter A. , Hardy-Bessard Anne-Claire , Denschlag Dominik , Pujade-Lauraine Eric , Ray-Coquard Isabelle Laure 
Published: June 2023

5550 Background: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), maintenance ola (a PARP inhibitor) + bevacizumab (bev) led to prolonged progression-free and overall survival vs placebo (pbo) + bev in AOC pts, specifically those with homologous recombination-deficient (HRD+) tumors (Ray-Coquard et al. ESMO 2022, LBA29). Here, we explore the efficacy of subsequent chemotherapy (CT) in pts after progression on first-line (1L) treatment in PAOLA-1. Methods: The efficacy of subsequent CT was explored by analyzing the median time from first subsequent therapy (FST) to second subsequent therapy (SST). Efficacy was compared by FST type, HRD status, and timing of progression (during/after ola). A multivariate Cox model was used in ola + bev pts to identify prognostic factors influencing time from FST to SST, including HRD status, platinum-free interval (PFI), clinical risk based on disease stage and surgical status, timing of progression, and response to 1L CT. All P values are exploratory. Results: In total, 544/806 (67.5%) pts progressed and received subsequent CT: 338/537 (62.9%) ola + bev pts and 206/269 (76.6%) pbo + bev pts. In the overall population and in the subgroup who received platinum-based combination therapy (PBC), time from FST to SST was shortest in pts who progressed during ola (Table). Pts who progressed after ola had similar outcomes to pbo + bev pts (Table). Efficacy was broadly consistent regardless of HRD status (Table). The multivariate analysis confirmed that progression after (vs during) ola prolonged time from FST to SST (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.50–0.84; P=0.0011) independently of other known prognostic factors, such as PFI ≥12 vs <12 months (HR 0.38, 95% CI 0.29–0.51; P<0.0001) or lower vs higher clinical risk (0.58, 0.42–0.81; P=0.0015). Conclusions: In this post hoc exploratory analysis of PAOLA-1, the efficacy of subsequent CT at relapse appeared dependent on whether progression occurred during or after the end of ola treatment. Efficacy was reduced when relapse occurred during ola but was comparable between pts who progressed after ola vs pbo + bev pts. Clinical trial information: NCT02477644 . [Table: see text]
BRCA1 and RAD51 methylation impact on outcome in patients with advanced ovarian cancer: A PAOLA-1 ancillary study.
Authors: Blons Helene , Abdelli Justine , Taly Valerie , Mulot Claire , Laurent Puig Pierre , You Benoit , Harter Philipp , Lorusso Domenica , Garcia Yolanda , Schauer Christian , Hietanen Sakari , Colombo Nicoletta , Vergote Ignace , Kobayashi Hiroaki , De La Motte Rouge Thibault , Buderath Paul , Cecere Sabrina Chiara , Bataillon Guillaume , Pujade-Lauraine Eric , Ray-Coquard Isabelle Laure 
Published: June 2023

5559 Background: The PAOLA-1/ENGOT-ov25 trial showed that adding olaparib (ola) to maintenance bevacizumab (bev) after first-line therapy led to a progression-free and overall survival benefit in advanced ovarian high-grade carcinoma (AOC) patients with homologous recombination deficiency (HRD) (Myriad MyChoiceR Genomic Instability Score) or BRCA1/2 mutations (BRCAmut). Here, we address the impact of BRCA1 and RAD51C epimutations to improve our understanding of GIS beyond BRCAmut. Methods: BRCA1 and RAD51C methylation analysis was assessed and quantified in pre-treatment biopsies (66%), after neoadjuvant chemotherapy (NACT) (20%) or unknown (14%) from bisulfite converted DNAs using fluorescent methylation specific PCR and methylation specific droplet digital PCR (ddPCR). Methylation status was correlated to clinical data, BRCA1/2 mutations, GIS and HRD scores, PFS (PFS1, PFS2) and OS. R (r-project.org) was used for statistical analysis. Results: Among the 537 patients randomized to maintenance ola + bev and 269 to placebo (pbo) + bev, 348 and 171 were available for methylation analysis. Their baseline molecular and clinical characteristics were well balanced with those of the entire cohort. Promoter methylation was identified in 67 (12.9%) samples for BRCA1 and 25 (4.8%) for RAD51C (4 were methylated on both genes). Methylation and BRCAmut were mutually exclusive except for 3 samples. Mean GIS scores were 62.5 [59.6-65.5]; 59.4 [57.2-61.5]; 54.2 [50.5-57.8]; 23.4 [21.6-25.2] for BRCA1 or RAD51C methylated ( met-tumors), BRCAmut, non-mut/non-met HRD+ ( b-/m-HRD+) and HRP (proficient) tumors respectively. Among met-tumors 92% (66/72) were GIS positive (>42). The mean GIS score of Met-tumors were significantly higher than that of b-/m- HRD+ samples (p=0,009). Benefit of adding ola maintenance to bev was in a similar between patients with met AOC and those with b-/m- HRD+ tumors ( table). Conclusions: Methylated BRCA1/RAD51 tumors are HRD+ and provide to ovarian cancer patients a similar clinical benefit of ola+bev as patients with b-/m- HRD+ tumors. Methylation assessment represents a rapid and cost effective tool; which coupled with BRCA1-2 somatic testing allows the identification of the majority (81%) of HRD+ AOC. Clinical trial information: NCT02477644 . [Table: see text]
Trends in ovarian cancer incidence and incidence-based mortality: A 15-year population-based analysis.
Authors: Somasegar Sahana , Reddy Ravali A. , Karam Amer 
Published: June 2023

5570 Background: The predicted incidence and incidence-based mortality (IBM) of ovarian cancer (OC) in 2023 is lower than prior years. OC encompasses a range of heterogeneous cancers with subtypes categorized on histology and site of origin. Given differences in survival and treatment paradigms, we aim to characterize trends in OC incidence and IBM based on histology and site of origin to determine what factors are responsible for the decline. Methods: Patients with OC from 2000-2019 were identified from the US Surveillance, Epidemiology, and End Results 17 registry database. Using ICD-O-3 codes, patients with epithelial, stromal, and germ cell cancers of the ovary, fallopian tube, and peritoneum were included. Incidence and IBM were reported as age-adjusted rates and stratified by cancer subtype. Using Joinpoint 4.9.1.0, we characterized piecewise log-linear time trends to identify inflection points in the rates’ annual percentage change (APC). Results: The incidence of epithelial OC decreased significantly from 2004-2019 (APC -1.24%). When stratified by disease stage, this trend was seen in distant disease (APC -2.11%) and unknown/unstaged disease (APC -3.40%); however, there was a significant increase in incidence of local disease (APC +0.83%). There was no significant change in the incidence of germ cell and stromal OC from 2004-2019 in all stages. (APC -0.30% and +0.33%). Among all OC subtypes, there was a significant decline in incidence from 2000-2019 (APC -1.57%) with a sharper decline from 2015-2019 (APC -3.41%). Among all cancer subtypes, the incidence trended down from 2000-2019, with a significant decline from 2015-2019 (APC -2.37%). Similar trends are observed in IBM. Among all stages of epithelial OC, there was a significant decrease in IBM from 2006-2019 (APC -2.02%). When stratified by disease stage, there was a decline in IBM in local disease (APC -7.19%, 2014-2019) and distant disease (APC -2.44%, 2010-2019). There were no changes in IBM of germ cell and stromal OC from 2004-2019 (APC +0.78% and -0.20%). Among all cancers, IBM significantly decreased from 2006-2019 (APC -2.28%). When stratified by disease stage, there was no change among local disease and an increase in regional disease from 2006-2019 with the increase from 2006-2010 (APC +14.35%) compared to 2010-2019 (APC +1.45%). Conversely, there was a significant decrease in IBM for distant disease (APC -2.51% from 2010-2019) and unknown/unstaged disease (APC -3.27% from 2006-2019). Conclusions: There has been an overall decline in incidence and IBM of OC over a 15-year period, primarily driven by the epithelial histology. Over the past 20 years, OC has been increasingly diagnosed at earlier stages with a corresponding improvement in survival. While stage migration and improved survival may contribute to these trends, they do not entirely explain them. As new treatments become available, the incidence and IBM of OC may further decline.