bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer: A phase II trial.
Authors: Wan Ting , Huang He , Feng Yanling , Li Jundong , Zheng Min , Meng Yifan , Liu Jihong 
Published: June 2024

5512 Background: The KEYNOTE 826 study has demonstrated significant survival benefits with first-line pembrolizumab (anti PD-1) plus chemotherapy for recurrent/metastatic cervical cancer (CC). This phase II study aims to evaluate the efficacy and safety of Sintilimab (anti PD-1) plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced CC. Methods: Patients with newly confirmed locally advanced CC (stage IB3 or IIA2) received neoadjuvant chemotherapy with paclitaxel (150mg/m2, iv) and cisplatin (70mg/m2, iv) plus Sintilimab (200mg, iv) Q3W for 3 cycles, followed by radical surgery. The patients evaluated PD without distant metastases after 2 cycles of neoadjuvant therapy underwent surgery immediately. The primary endpoint was pathological complete remission rate (pCR). Secondary endpoints included ORR, PFS, 2-years PFS rate and adverse events (CTCAE 5.0) and biomarker exploration. Results: As of data cutoff on Feb 1st, 2024, 47 eligible patients were enrolled, 44 patients received 3 cycles of neoadjuvant therapy, 43 patients then underwent radical surgery and were evaluable. The primary endpoint of pCR rate was 32.6% (14/43), optimal remission rate (residual tumor cells with a depth of less than 3mm) was 51.2% (22/43). Except for one patient with SD, 42 had objective responses (97.7%). At the date cutoff, the median follow-up time was 17 months (range 1-35), two patients who evaluated as PR after neoadjuvant therapy were recurred, one with distant lymph node recurrence, and the other with lung metastasis. In terms of hematological toxicity, 15 patients presented with grade 3-4 neutropenia and no other grade 3-4 adverse events. Possible immune-related side effects included skin rash (17/47, G1-2), alanine aminotransferase increased (8/47, G1), hypothyroidism (6/47, G1-2), creatinine increased (5/47, G1), and hyperlipidemia (1/47, G1). Conclusions: Sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy showed encouraging antitumor activity with 32.6% pCR rate and manageable toxicities in patients with locally advanced CC. Clinical trial information: NCT04799639 .
Combination of cemiplimab and ISA101b vaccine for the treatment of recurrent/metastatic HPV16 cervical cancer.
Authors: Lorusso Domenica , Oaknin Ana , Santos Borges Giuliano , Damian Fernanda , Ottevanger P. B. , Van Gorp Toon , Paiva Carlos Eduardo , Kroep Judith R. , Kim Yong Man , Kim Hee Seung , Lee Jae-Kwan , Melief Cornelis JM , Hooftman Leon , Jamil Shaheda Jamil , Yoo Suk-Young , Seebach Frank A. , Lowy Israel , Fury Matthew G. , Mathias Melissa Divya , Colombo Nicoletta 
Published: June 2024

5522 Background: Cemiplimab + ISA101b vaccine is being studied in HPV16-positive cancers in several phase 2 clinical trials. Here, we present the clinical efficacy and safety results of a phase 2 study of cemiplimab + ISA101b vaccine in patients with recurrent HPV16 cervical cancer who had disease progression after first-line chemotherapy (NCT04646005). Methods: Patients received cemiplimab 350 mg administered intravenously every 3 weeks + 3 doses of ISA101b vaccine 100 µg/peptide administered by subcutaneous injection on Days 1, 29, and 50. The primary endpoint was objective response rate (ORR) as measured by RECIST version 1.1. Secondary endpoints included duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety. Efficacy and safety endpoints were assessed in the full analysis set (patients who received ≥1 dose). Baseline PD-L1 expression was assessed by immunohistochemistry using anti–PD-L1 clone SP263. Results: This single arm study included 113 patients (Table). Median duration of follow-up was 4.9 months (interquartile range [IQR]: 3.0–7.5); median duration of treatment exposure was 10.0 weeks (IQR: 9.7–10.3) for ISA101b and 18.2 weeks (IQR: 9.0–27.6) for cemiplimab. At data cutoff (May 22, 2023), 90 patients discontinued treatment for reasons including disease progression (66.4%), death (7.1%), and an adverse event (AE; 3.5%) and 20.4% of patients were still on treatment. ORR (95% CI) was 16.8% (9.9–23.7). ORR by PD-L1 expression in tumor cells was 12.5% for patients with PD-L1 <1% and 22.4% for patients with PD-L1 ≥1%, per investigator assessment. Median (95% CI) DOR was 5.6 (3.5–not estimable) months. Median (95% CI) OS and PFS were 13.3 (10.8–16.3) months and 3.0 (1.7–4.0) months, respectively. At 6 and 12 months, the estimated survival probabilities (95% CI) were 80.5% (71.7–86.9) and 54.5% (42.1–65.3), respectively, for OS, and 20.5% (13.4–28.6) and 7.8% (3.3–15.0), respectively, for PFS. Treatment-emergent AEs occurred in 92.9% of patients, with the most common being injection-site reaction (38.9%), anemia (25.7%) and nausea (22.1%). Six (5.3%) patients died due to a treatment-emergent AE. Conclusions: Results from this phase 2 study of cemiplimab + ISA101b in patients with recurrent HPV16 cervical cancer show clinical benefit, especially in patients with high PD-L1 expression, and no unexpected safety signals, supporting further research. Clinical trial information: NCT04646005 . [Table: see text]
Specific vaginal and gut microbiome and the anti-tumor effect of butyrate in women with cervical cancer.
Authors: Han Mengzhen , Feng Yun , Zhou Yuhang , Han Li , Liu Xiaolin , Sun Tao , Xu Junnan 
Published: June 2024

5529 Background: To investigate the vaginal and gut microbes changes during the carcinogenesis of cervical and the auxiliary diagnostic value of microbial markers. To investigate the effect of microbiome-specific metabolites butyric on cervical cancer cells. Methods: We studied 416 vaginal 16S rRNA sequencing data and 116 gut data. Reads were processed using VSEARCH. We used Shannon index, Chao1 index, Simpson diversity index, Beta diversity index, LEfSe analysis, co-abundance network analysis and KEGG enrichment analysis to explore microbiome differences between groups. We constructed random forest models based on genus and validated the models to test their diagnostic effectiveness. Finally, we used the cell counting kit-8 (CCK-8) method to detect cell proliferation capacity and flow cytometry to detect apoptosis and induction of cell cycle progression. Results: Compared to the non-cancerous population, patients with cervical cancer had unique microbial community characteristics in both vaginal and gut ecological niches. Our predictive model based on genus in two ecological regions achieved high accuracy in the diagnosis of cervical cancer (vaginal model AUC=91.58%; gut model AUC=99.95%). Potential functional pathways analysis indicated significant differences between the normal women microbiomes and cervical cancer women microbiomes. Butyric inhibited cervical cancer cell proliferation in a concentration-dependent manner and promoted apoptosis of cancer cells. Conclusions: Significant differences were found in vaginal and gut microbes in patients with cervical cancer compared to the non-cancerous population, and the microflora is involved in cervical carcinogenesis. The prediction models constructed at the genus level in both ecological sites have good diagnostic value for cervical cancer. Microorganisms may be involved in cervical cancer progression in a metabolite-dependent way, and targeting butyric may provide therapeutic options for cervical cancer.
The efficacy of recombinant human adenovirus type 5 (H101) intra-tumor therapy in persistent/recurrent/metastatic gynecological cancer and the exploration of changes in tumor microenvironment.
Authors: Zhang Qiying , Liu Zi , Zhang Jing , Wang Fei , Fan Shi , Wang Juan , Wang Tao , Su Jin 
Published: June 2024

5536 Background: Previous small sample retrospective study has showed that H101 has promising efficacy and favorable safety in patients with persistent /recurrent/metastatic (P/R/M) gynecological cancer. To further assess the effecacy and safety of H101 in P/R/M gynecological cancer, we conducted this prospective Phase II study and further explore the tumor microenvironment (TME) through Cell DIVE multiplexed imaging solution. Methods: This was a prospective, open-label, single-arm study (clinicaltrials.gov number NCT05051696). P/R/M gynecological cancer patients who had at least one injectable lesion and had received at least one line of systemic therapy or could not tolerate chemotherapy were eligible. H101 (0.5-1.5×1012 viral particles) was injected into the target lesion once a day for 5 consecutive days, with a cycle of 3 weeks and a maximum of 4 cycles. Whether added other medications was at the physician’s discretion. Cell DIVE multiplexing of 15 immune cell markers were performed in 6 paired pre- and post-H101 injected tumors. Results: From September 2021 to February 2024, 116 P/R/M patients received H101 intro-tumor injection, of which 16 patients did not evaluate for the efficacy endpoint. At the data cut-off of February 2024 for the primary analysis, overall median follow-up time was 10 months. The best complete response was achieved in 30 patients, 34 patients achieved partial response and 15 patients had stable disease, yielding an objective response rate of 64%. The disease control rate was 79% by RECIST1.1, and the median duration of time was 7.1 months. The median progression-free survival was 8.7 months, and the median overall survival was currently not reached. Furthermore, 83% of the patients experienced treatment-related adverse events and the major adverse events were fever (64%), fatigue (31%) and pain at the injection site (25%). Compared with baseline, the number of B cells, T regulatory cells and Ki 67+ tumor cells decreased in the injected lesions, while the number of M1 macrophage, monocytes, CD4 and CD8 T cells were increased. Additionally, B cells and CD68+CD163- tumor associated macrophage (M1 TAM) were higher in response patients. Conclusions: This was the first reported large sample size prospective study regarding H101 in gynecological cancer. These results indicated that H101 as second line or later therapy for P/R/M gynecological cancer patients was efficacious and safe. Cell DIVE multiplexing of immune cell markers suggested that the H101 efficiently reshaped the TME and the response of H101 oncolytic virotherapy may associated with increased B cells and M1 TAM in the TME. Clinical trial information: NCT05051696 .
Tumor-informed ctDNA as an objective marker for postoperative residual disease in epithelial ovarian cancer.
Authors: Paspalj Valentina , Grimm Christoph , Postl Magdalena , Tauber Christina Viktoria , Segui Nuria , Brueffer Christian , Alcaide Miguel , Oton Lucia , Chen Yilun , Saal Lao H. , Hofstetter Gerda , Muellauer Leonhard , Kessler Mirjana , Trillsch Fabian 
Published: June 2024

5544 Background: The most important predictor of prognosis in patients with high-grade serous ovarian cancer (HGSOC) is complete tumor resection after primary surgery. The current practice for classifying postoperative residual disease is the subjective assessment by the physician at the end of surgery. To date, an accurate objective marker for postoperative tumor residuals is lacking. In this study we are evaluating circulating tumor DNA (ctDNA) as a predictive marker for postoperative minimum residual disease (MRD). Methods: In this prospective multi-center feasibility study, we included 52 patients with advanced HGSOC who underwent primary debulking surgery between July 2021 and December 2023. Intraoperatively, tumor tissue from several tumor locations was evaluated. Blood samples were examined preoperatively, on day two, and day ten postoperatively. Whole genome sequencing (WGS) was used to identify structural variants (SVs), single nucleotide variants (SNVs) and indels in fresh frozen or FFPE tumor tissue to develop personalized multiplex digital polymerase chain reaction (dPCR) fingerprint assays. Results: A high burden of SVs was detected (median 90 SVs, range 24-287) and dPCR assays successfully designed and orthogonally validated in all tumor samples. A unique dPCR fingerprint was generated for every patient, tracking one to eight biomarkers per patient (median 8). In a subset of 10 patients tissue biopsy samples from multiple tumor localizations were available. The personalized fingerprint was validated across all locations and shown to be consistent. In the overall cohort, ctDNA was positive in 96% (n=46/48) of patients preoperatively and in 87% (n=39/45) at postoperative day 10 (d10), when a plasma sample was available. Compared to patients without macroscopic residual disease, patients with postoperative tumor residuals expressed significantly higher ctDNA levels at d10 (p <0.001). Furthermore, for patients with macroscopic tumor residuals, ctDNA levels at d10 (% variant allele fraction (VAF)) remained comparable to preoperative ctDNA levels (4% decrease in median ctDNA levels). In contrast, patients with macroscopic complete resection were noted to have a 97% decrease in median ctDNA levels between pre-operative and d10 detection. Conclusions: The present tumor-informed dPCR SV fingerprint ctDNA approach demonstrated feasibility with remarkably high detection rates pre- and postoperatively. Postoperative ctDNA levels differed substantially based on postoperative tumor residuals. These findings suggest that this personalized approach could be used to develop a dPCR SV detection assay and may have clinical utility for postoperative MRD evaluation in patients with primary advanced HGSOC.
Gemcitabine plus cisplatin in recurrent ovarian, fallopian tube, and primary peritoneal cancer.
Authors: Eyada Mostafa , Fellman Bryan M. , Patel Shrina , Michael Victoria , Soliman Pamela T. , Sims Travis T. , How Jeffrey Andrew , Jazaeri Amir A. , Fleming Nicole D. , Ramondetta Lois M. , Westin Shannon Neville 
Published: June 2024

5548 Background: Our objective was to explore safety and efficacy of gemcitabine plus cisplatin for treatment of patients with recurrent ovarian, fallopian tube and primary peritoneal cancer (OC). Methods: This single institution retrospective analysis conducted at MD Anderson Cancer Center, included patients with recurrent platinum sensitive (PSOC) or resistant (PROC) OC treated with gemcitabine plus cisplatin. Treatment doses were cisplatin 30-40 mg/m2 and gemcitabine 600-800 mg/m2. Utilized regimens were as follows: 1) cisplatin Day 1 (D1), gemcitabine D1 on 21-day cycle; 2) cisplatin D1, gemcitabine Day 8 (D8) on 21-day cycle; or 3) cisplatin/gemcitabine every 2 weeks on 28-day cycle. Objective response rate (ORR= complete response (CR) + partial response (PR)) was calculated along with 95% confidence interval (95%CI). Adverse events were collected and graded. Results: One hundred and seventy-six patients were included; 90% had high grade serous OC and 95% were stage III/IV at diagnosis. Subjects received a median of 3 prior lines of therapy (range 1-10). ORR was 44.1% (95% CI: 36.6-51.9) with 12 CR (7%), 64 PR (37%), 42 SD (24%) and 54 PD (31%). One hundred sixteen (66.6%) patients discontinued treatment due to disease progression after median 3 cycles (range 1-19). Among responders, median number of cycles with response was 3 (range 2-13). Twenty-three percent of subjects had PSOC with ORR of 61.5% and 76.1% had PROC with ORR of 39.4% (p =0.014). Number of prior lines of cytotoxic treatment or prior use of bevacizumab wasn’t associated with response to treatment. Median platinum free interval was associated with response to therapy (5 months in responders vs 3 months in non-responders; P=0.007). Forty-four percent of patients had adverse events, with most common being thrombocytopenia (12%), neutropenia (9%), and neurotoxicity (10%). Conclusions: Cisplatin in combination with gemcitabine demonstrates activity regardless of platinum sensitivity status in patients with recurrent ovarian cancer. However, longer platinum-free interval is associated with improved response to this therapy.
Evaluation of a novel extracellular vesicle (EV) based ovarian cancer (OC) screening test in asymptomatic postmenopausal women.
Authors: Manning Brendan , Banerjee Sanchari , Bortolin Laura T , Winn-Deen Emily S. , Hamzeh Bilal , Grimes Brittany , Santos-Heiman Timothy , Byrne Delaney M. , Hawkins Troy B , King MacKenzie Sadie , Salem Daniel P. , Smith Michael , Apostolidou Sophia , Gentry-Maharaj Aleksandra , Berg Christine D. , Skates Steven , Ransohoff David , Guettouche Toumy , Mattoon Dawn R , Menon Usha 
Published: June 2024

5553 Background: Screening for OC that relies on CA125 and imaging lacks early-stage sensitivity, highlighting the need for a more effective test. EVs in blood may provide increased sensitivity from vesicles released in abundance and increased specificity from assessing multiple cancer-related markers colocalized on a vesicle surface. We report performance of an EV based OC Test in samples from asymptomatic postmenopausal women in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods: The OC Test (biomarkers, classifier, cutoff) was locked following a training study, after which we observed consistent assay performance in an independent cohort. Here we evaluated the OC Test in a blinded case-control study nested within the no screening (NS) and annual ultrasound screening (USS) arms of UKCTOCS. Cases were all women with a diagnosis (Dx) of high-grade serous carcinoma (HGSC) within 36 months following sample donation and were matched 10:1 by age at collection to women who had no OC detected before or within the trial follow up period (controls). In addition, samples drawn within 6 months prior to a false positive (FP) transvaginal ultrasound from women who underwent surgery for benign findings in the USS arm were evaluated. OC Test and research use CA125 test at previously established 98% specificity cutoff, were determined blinded to case-control status, with unblinding done by UCL only after all tests were completed. Results: We assessed 129 samples from women with HGSC, 1310 controls and 100 USS FP samples. Data from 160 samples were excluded due to operator error, low sample volume or quality issues. In healthy controls, we observed a 97.7% specificity for the OC Test, and 95.5% for CA125, P = 0.006 McNemar test. We observed a sensitivity of 82% for the OC Test in samples drawn 0-12 months prior to Dx, and 63% for CA125, P = 0.016 McNemar test. Additionally, only 2.3% (2/86, 95% CI 0.3-8.1) women who underwent surgery for false positive USS results were positive for the OC Test vs 10.4% (9/86, 95% CI 4.9-18.9) for CA125. Conclusions: The OC Test is capable of highly sensitive and specific detection of HGSC in asymptomatic postmenopausal women one year prior to Dx and can detect HGSC up to three years prior to Dx with superior sensitivity and specificity compared to CA125. The data supports further evaluation of the OC Test for OC screening. [Table: see text]
Anlotinib plus hormone therapy in patients with platinum-resistant recurrent ovarian cancer: A prospective, single-arm, open-label, phase II study.
Authors: Wang Xipeng , Li Jiarui , Zhang Ping , Wang Yizhi , Lu Xin , Xu Hong 
Published: June 2024

5567 Background: Studies have suggested that estrogen regulates the malignant transformation of ovarian surface epithelial cells, stimulates the growth and migration of cancer cells. and promotes the VEGF expression in epithelial ovarian cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling. In this study, we evaluate the activity of anlotinib combined with letrozole in patients with estrogen receptor positive, platinum-resistant recurrent ovarian carcinoma (NCT04720807). Methods: Patients who have previously received two or more chemotherapy treatments, with histopathologically confirmed high-grade serous ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), estrogen receptor (ER) positive and ECOG 0-2 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and letrozole was taken orally (2.5mg qd, d1-21, 21 days per cycle). 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), duration of remission (DOR) progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2020 and December 2023, 30 patients with a median age of 61 years (range:50-79), FIGO histopathological stage I (11.1%), Ⅱ(3.7%), III (59.3%) and IV (25.9%) were enrolled. Twenty-seven of these patients have been evaluated for efficacy. In the efficacy-evaluable population (n=12), the therapeutic evaluation showed that 7 and 13 patients achieved partial response and Stable disease respectively(with the standards of GCIC), yielding the ORR of 16.7% (7/27 95% CI: 11.8% to 46.6%). The DCR was 74.1% (20/27, 95% CI: 53.4% to 88.1%). The median PFS was 4.24 months (95% CI: 3.71m to 5.09m) and the median OS was 18.96 months (95% CI: 8.34m to 31.05m).With subgroup analyses, Patients who had received PARPi before and patients with baseline CA125 level >500 had significant prolongations in mOS and mPFS, respectively. The most common adverse events (AEs) were grade 1 or 2, which included laryngitis (44.4%), stomatitis (37.0%), hand-foot syndrome (29.6%), and fatigue (25.9%), diarrhea (22.2%), hypertension (14.8%),. The grade 3 AEs were hypertension (37.0%), hand-foot syndrome (3.7%), diarrhea (3.7%) and hyperuricemia (3.7%). No higher AEs or treatment-related death were observed. Conclusions: As a chemo-free regimens, anlotinib plus letrozole showed a promising efficacy with a favorable toxicity profile for patients with platinum-resistant recurrent ovarian cancer. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co. GYNECOLOGIC CANCER. Clinical trial information: NCT04720807 .