bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and analytical validation for HRD status using targeted panel sequencing.
Authors: Bao Hua , Liu Rui , Tang Haimeng , Wu Xuxiaochen , Chen Xiaoxi , Wu Yong , Wu Xue , Shao Yang 
Published: July 2024

e17501 Background: In cancer therapy, understanding homologous recombination deficiency (HRD) is paramount, particularly due to its positive association with sensitivity to PARP inhibitor (PARPi) therapy. We propose using a targeted sequencing approach as a cost-effective and efficient alternative to the current standard of whole genome sequencing (WGS). In this study, we determine the sensitivity and clinical applications of a panel of 437 genes and over 12000 heterozygous SNP loci for evaluating HRD. Methods: HRD positivity for this assay was set at an HRD score of ≥38. To determine the limit of detection (LOD), we diluted 19 samples (4 tiers, 20 repeats each) with known HRD status. Accuracy of the assay was determined by comparing HRD status calls of 40 samples with those obtained through whole genome sequencing. Reproducibility of the assay was tested by measuring variance of HRD status for 30 samples between experimental conditions (2 operators* 3 repeats). Samples were obtained from 85 ovarian cancer (OC) patients undergoing platinum-based (Pt) chemotherapy and were profiled using our targeted sequencing assay. Results: The LOD for BRAC1/2 copy number deletions was established at a tumor purity (TP) of 30%. On the level of individual mutations, LODs range between 1.74% to 5.85% AF with a median of 2.26% AF. Repeatability analysis yields high concordance (APA= 97.83%, 95%CI= 95.34% - 99.00%; ANA= 97.73%, 95%CI= 95.13% - 98.95%), which emphasizes the precision of the assay. Comparisons against WGS based HRD scores reveal strong correlations, with Pearson coefficients of 0.975 for single sample (tumor sample only) and 0.987 for paired sample (tumor + normal sample) HRD score analysis. Through tumor profiling, we identified novel gene mutations associated with resistance to PARPi therapy in the HRD-positive population of our cohort. In the clinical setting, HRD-positive OC patients were found to experience longer progression free survival than their HRD-negative counterparts (median PFS = 18.3 vs 11.4 months, p<0.05). Upon further investigation, we observed that HRD-positive patients who did not carry pathogenic alterations on BRCA1/2 gene showed significantly longer PFS than HRD-negative patients without pathogenic BRCA1/2 alterations (median PFS = 18.5 vs 11.6 months, p<0.05). Conclusions: In summary, this targeted panel offers enhanced sensitivity, reliability, and precision in the assessment of HRD status for informed cancer therapy decisions. In practice, we showed that the targeted sequencing approach is a viable solution for determining HRD status of OC patients and can potentially serve as a predictive biomarker for treatment response. We believe that out assay emerges as a cornerstone in the advancement of personalized cancer care, and offers a sensitive, reliable, and precise approach to HRD assessment for improving patient outcomes.
White blood cell kinetics in patients with gynecologic cancer receiving mecapegfilgrastim prophylaxis: A multicenter real-world study.
Authors: Chen Yong , Chen Liang , Li Gang , Zuo Li , Cheng Gang , Xu Nong , Mao Chenyu , Shen Peng , Chen Minbin , Wang Yanhong , Wang Zhanggui , Zhao Rusen , Bie Jun , Zheng Weie , Yan Haijiao , Zhang Guifang , Yang Zhe , Zhang Ningling , Xu Rui-Hua , Huang Xin 
Published: July 2024

e17502 Background: Some studies have indicated that using granulocyte-colony stimulating factor (G-CSF) following chemotherapy in patients with solid tumors may increase the risk of excessive white blood cell (WBC) elevation. In this real-world study, we aimed to assess the changes in WBC counts after prophylactic administration of 6 mg mecapegfilgrastim (a long-acting G-CSF) in multiple chemotherapy cycles among Chinese gynecological cancer patients, with a particular focus on those with low body weight (≤50 kg). Methods: A multicenter prospective cohort study was conducted involving gynecological cancer patients who received at least two consecutive chemotherapy cycles with mecapegfilgrastim 6 mg (administered 24 hours post-chemotherapy) between October 2019 and November 2021. Absolute WBC and absolute neutrophil counts (ANC) were recorded at baseline and on the 7th and 14th days of each cycle. Results: A total of 256 gynecological cancer patients completing 2-4 treatment cycles, including 86 with cervical cancer, 136 with ovarian cancer, and 34 with endometrial cancer, were analyzed. Of them, 58 had a pre-chemotherapy body weight of ≤50 kg, and 198 had a body weight of >50 kg. The majority of patients received taxane-based chemotherapy regimens with a cycle duration of ≥14 days. For day 7 post-chemotherapy WBC counts, data were collected from 535 cycles, including 125 cycles in the ≤50 kg group and 410 cycles in the >50 kg group. Elevated WBC counts (>10.0×10^9/L) were observed in 56 cycles (44.8%) in the ≤50 kg group and 177 cycles (43.2%) in the >50 kg group. On day 14 post-chemotherapy, data from 505 cycles, comprising 115 cycles in the ≤50 kg group and 390 cycles in the >50 kg group, indicated elevated WBC counts in 27 cycles (23.5%) in the ≤50 kg group and 63 cycles (16.2%) in the >50 kg group. In the ≤50 kg group, 3 cases (5.2%) experienced an ANC <0.5×10^9 /L, with no febrile neutropenia observed. In the >50 kg group, 11 cases (5.6%) experienced an ANC <0.5×10^9 /L, with 1 patient (0.51%) experiencing febrile neutropenia. Conclusions: In patients with low body weight (≤50 kg), the administration of 6 mg mecapegfilgrastim effectively stabilizes WBC elevation, exhibiting a favorable safety and efficacy profile. This regimen ensures the timely and appropriate progression of patients to subsequent cycles of chemotherapy. WBC counts in patients. [Table: see text]
CRS-HIPEC following neo-adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy in primarily advanced inoperable epithelial ovarian cancer: An ISPSM collaborative study.
Authors: Somashekhar S.P. , Chandrashekar Rohit Kumar C. , Rajgopal Ashwin K. , Fernandes Aaron Marian , Shanbhag Esha , Rakshit Susmita , Ahuja Vijay Kumar 
Published: July 2024

e17504 Background: PIPAC has shown improved objective response rate with improved quality of life in combination with IV chemotherapy when compared to IV chemotherapy alone in salvage situations. Methods: All patients with primarily inoperable advanced epithelial ovarian cancer not been able to receive optimal IV chemotherapy or not responding to first line of chemotherapy who could not undergo CRS-HIPEC were challenged with PIPAC & IV chemotherapy as a salvage situation after discussion in MDT. Patients who subsequently underwent CRS-HIPEC were analysed to study their clinical characteristics, extent of disease and peri-operative outcomes. PIPAC was given with Cisplatin 15mg/m2 and doxorubicin 3mg/m2. Intravenous chemotherapy was given within one week of PIPAC. Each cycle was repeated once in 4-5 weeks. Patients who underwent subsequently CC0 cytoreduction got HIPEC with Injection cisplatin 100mg/m2. All outcomes were prospectively entered in the registry and analysed retrospectively. Results: 120 PIPAC applications were done in 45 patients. 30 patients received 3 cycles of PIPAC with IV chemotherapy given within one week of PIPAC. Mean PCI initially was 25±5 with nearly 55% of them having ECOG 2 performance status and mean ascities volume of 500±55 ml . Out of 45 patients 28 underwent CRS-HIPEC subsequently. Mean age 54.5±10.74, PCI 15±5, duration of surgery 9.6±1.2 hrs. The mean drop in PCI who completed 3 PIPAC with IV chemotherapy was 10±3. Out of 45 patients nearly 60% showed PRGS 1, 25% PRGS 2 and 15% PRGS 3. 30.4% had total peritonectomy, 12.7% had multivisceral resection, 30% required diaphgramatic resections, 25%required mesentric stripping, 45.8% had one bowel resections and stoma rate was 4.5%. Overall G3-G5 morbidity was 25.4% with major ones being post-operative intra-abdominal collection (21.8%), electrolyte imbalance (16.4%), pulmonary (16.4%) followed by hematological (12.7%). The 30 day mortality was 3.8%. During PIPAC + IV chemotherapy no significant grade 3-4 morbidity was seen. Conclusions: Neo-adjuvant PIPAC with Intravenous chemotherapy might be a promising combination for inducing good response rates in advanced epithelial ovarian carcinoma. CRS-HIPEC following neo-adjuvant PIPAC + IV chemotherapy is safe, feasible and tolerable. PIPAC repeated every 4-5 weeks along with systemic chemotherapy provides a ideal scenario to monitor & assess response to loco regional and systemic chemotherapy.
Anlotinib combined with penpulimab as first-line treatment for persistent, recurrent, or metastatic cervical cancer: Preliminary results from ALTER-GO-020, a single-arm, open-label, multi-cohort, multi-center phase II clinical study.
Authors: Wang Dengfeng , Liu Hong , Chen Lihong , He Mian , Zhao Weidong , Xiang Yang , Zhang Guonan 
Published: July 2024

e17506 Background: The BEATcc trial demonstrated the combination of atezolizumab plus bevacizumab and platinum regimen as first-line treatment for recurrent, or metastatic cervical cancer significantly improves progression-free survival (PFS) and overall survival (OS) regardless of PD-L1 status. ALTER-GO-020 is an ongoing open-label, single-arm, multi-cohort phase II study evaluating the combination of anlotinib (a multitarget anti-angiogenic TKI) and penpulimab (anti-PD-1 antibody) as a chemotherapy-free regimen for patients (pts) with recurrent or metastatic gynecological cancer. Here, we report the preliminary results of the cohort of patients with recurrent or metastatic cervical cancer from ALTER-GO-020. Methods: Eligible pts were histologically confirmed persistent, recurrent, or metastatic cervical cancer (including adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma), not amenable to curative treatment, and had no prior systemic treatment for metastatic, persistent, or recurrent disease. Pts were treated with anlotinib (12mg, po qd, d1-14, q3w) plus penpulimab (200mg, IV, d1, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included PFS, duration of response (DOR), disease control rate (DCR), OS and safety. Results: From May 2022 to Nov 2023, 17 pts were enrolled. The median age was 52 years (range, 31-70), 65% of pts were squamous-cell carcinoma, 88% received previous chemoradiotherapy with or without surgery, and 71% had previously received neoadjuvant/adjuvant platinum-containing chemotherapy. As of date cutoff (Dec, 2023), the median follow-up time was 6.8 months (range, 1.4-18.3 months). In the efficacy analysis (n=17), the preliminary ORR was 58.8% (95% CI: 32.9%-81.6%), DCR was 88.2% (95% CI: 63.6%-98.5%). The mPFS was 11.0 months (95% CI: 5.4-16.7 months). The mOS was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in all 17 pts, in which 8 (47.1%) were grade ≥3. The most common grade ≥3 TRAEs were hypertension (29.4%), hand foot syndrome (11.8%), fatigue (11.8%), and diarrhea (5.9%). TRAEs led to dose reduction and interruption were 29.4%, and 35.3% of pts, respectively. No TRAEs leading to death. Conclusions: The preliminary results demonstrated that anlotinib plus penpulimab as a first-line therapy for persistent, recurrent, or metastatic cervical cancer showed promising antitumor efficacy and manageable safety profile. Clinical trial information: NCT05028504 .
Zimberelimab combined with concurrent chemoradiotherapy for patients with locally advanced cervical cancer: Early results of efficacy and safety.
Authors: Lin Genlai , Ma Guifen , Wang Sitong , Xiao Chunli , Shi Tingyan , Xiang Libing , Jiang Li , Du Shisuo , Zeng Zhaochong 
Published: July 2024

e17507 Background: To assess the efficacy and safety of zimberelimab combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) patients (pts). Methods: This a single arm, open label, prospective phase II study. participants aged 18-75 years of FIGO 2018 IIB-IVA LACC, with histologically confirmed adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma untreated with radiotherapy or immunotherapy for cervical cancer were included. Nineteen enrolled pts received zimberelimab (240 mg, IV, Q2W) for up to one year starting from the first week of radiotherapy, combined with CCRT, including cisplatin (25-40 mg/m2), paclitaxel (35 mg/m2), once a week for up to 5 cycles, intensity modulated radiation therapy (IMRT, 45-50 Gy/25-28 f), with a simultaneous integrated boost of 10-15 Gy to involved metastatic lymph nodes, followed by brachytherapy (30-40 Gy, 5-6 Gy/f, biw). All radiotherapy was completed within 8 weeks. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), 3-year overall survival (OS) rate and safety. Results: The median age was 57 years (range, 32 to 71), with 6 pts in stage IIB, 2 pts in stage IIIB, 8 pts in stage IIIC, and 3 pts in stage IVA. All pts completed CCRT successfully, with 18 pts completed 5 cycles of chemotherapy, while only 1 pts received 4 cycles of chemotherapy. The median cycles with zimberelimab treatment was 15 (range, 6 to 26). Grade (G) 3 and higher treatment related adverse events (TRAEs) were observed in 13 pts (13/19, 68.4%), 1 pts had G4 lymphopenia (1/19, 5.3%). The most frequent ≥G3 TRAEs was lymphopenia (11/19, 57.9%), followed by leukopenia (7/19, 36.8%). The ORR was 100%, with complete responses in 18 pts (18/19, 94.7%) and partial responses in 1 pts (1/19, 5.3%). At data cutoff (October 31, 2023), 2 pts had disease progression (2/19, 10.5%), 17 pts have been remaining in disease remission (17/19, 89.5%). Conclusions: Zimberelimab combined with CCRT achieved promising anti-tumor effects and manageable toxicities in LACC pts. Further follow-up results are expected. Trial registration: ClinicalTrials.gov Identifier: NCT05437692. Clinical trial information: NCT05437692 . [Table: see text]
Immunotherapy-based neoadjuvant therapy followed by concurrent chemoradiotherapy in locally advanced and advanced cervical cancer: A real-world study.
Authors: Wei Qianxue , Qu Hui , Gong Tingting , Gao Song , Tian Nan , Li Xiuqin 
Published: July 2024

e17509 Background: Locally advanced and advanced cervical cancer (CC), characterized by extensive local invasion and potential distant metastasis, present substantial clinical challenges. Although concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced CC, a considerable proportion (23%-34%) of treated pts experienced recurrence or subsequent metastasis. Recently, neoadjuvant therapy (NAT) has been proposed to increase the radiosensitivity and decreases the fraction of hypoxic cells. Particularly, immunotherapy (IO)-based NAT has shown high activity in treating CC. Moreover, IO plus CRT has shown promise in enhancing both local control and systemic response. Hence, we analyzed the efficacy and safety of IO-based NAT followed by CCRT for locally advanced and advanced CC in a real-world setting. Methods: This study retrospectively analyzed data from pts with locally advanced and advanced CC who underwent IO-based NAT followed by CCRT at Shengjing Hospital of China Medical University from January 2022 to January 2024. Outcome measures included complete response (CR), partial response (PR), objective response rate (ORR), progression free survival (PFS), and safety. Tumor responses after neoadjuvant or CCRT therapy were evaluated using RECIST v1.1 and PFS was analyzed with the Kaplan-Meir method. Safety was assessed by adverse events (AEs) referring to CTCAEs v 5.0. Results: A total of 20 pts (median age 57 years, range, 39-72) were included in this analysis, with 15% at stage IIIB, 60% at IIIC, 10% at IVA, and 15% at IVB. Eight (40%) pts received 1 cycle of neoadjuvant IO, 8 (40%) received 1-4 cycles of neoadjuvant IO + chemotherapy, and 4 (20%) received 2 cycles of neoadjuvant IO + bevacizumab (Bev) + chemotherapy. After NAT, all 20 pts received CCRT. In the overall population, ORR after NAT was 55% (11/20), with 5% CR and 50% PR. Regarding different IO-based NAT regimens, objective responses were achieved in 1 of 8 (12.5%) pts receiving neoadjuvant IO, 6 of 8 (75%) pts receiving neoadjuvant IO + chemotherapy, and 4 of 4 (100%) pts receiving neoadjuvant IO + Bev + chemotherapy. After CCRT, 6 (30%) pts had a CR and 7 (35%) pts had a PR, resulting in an ORR of 65.0%. At a median follow-up of 14.9 months, the median PFS was not reached, with a 12-month and 24-month PFS rates of 68% and 56%, respectively. The most common treatment-related AEs during NAT were white blood cell count decreased (50%) and neutrophil count decreased. Conclusions: IO-based NAT followed by CCRT were effective and well-tolerated for pts with locally advanced and advanced CC. This treatment modalities may provide a potential therapeutic strategy for locally advanced and advanced CC.
Cadonilimab safety and efficacy in recurrent or metastatic cervical cancer: First real-world experience from a Chinese multicenter study.
Authors: Sun Yang , Chen Jian , Yu Haijuan , Fan RenLiang , Liu Li , Xiao Weixiong , Lin Rong , Chen DeZhao , Weng Xiaoying , Shen Fengfang , Wang Shaoyu , Tian Qihua , Zeng Wei , Lian Rong 
Published: July 2024

e17510 Background: Cadonilimab, a bi-specific antibody that simultaneously targets PD-1 and CTLA-4, was approved on 29 June 2022 in China for the treatment of recurrent or metastatic cervical cancer (R/M CC) in patients who have progressed following platinum-based chemotherapy. The COMPASSION-03 trial recently demonstrated promising tumor response rates with cadonilimab in R/M CC patients. This study aims to assess the efficacy and safety of cadonilimab in a real-world clinical setting in China. Methods: This multicenter retrospective study enrolled 102 patients with R/M CC, who received at least one cycle of cadonilimab at seven medical centers from July 2022 to October 2023. Among these, 94 patients were administered 10 mg/kg of cadonilimab once every 3 weeks on day 1, while 8 patients received 6 mg/kg every 2 weeks on day 1. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and the disease control rate (DCR) of the overall patients, as well as toxicity, were evaluated. Results: The study included patients with squamous cell carcinoma (73 patients), adenocarcinoma (20), adenosquamous carcinoma (5), and small cell neuroendocrine carcinoma (4). The median age was 54 years, ranging from 28 to 83. Initially, most patients presented with advanced disease: stage IIIB (8 patients), stage IIIC (24), and stage IV (43). The Eastern Cooperative Oncology Group (ECOG) performance status was 0, 1, 2, and 3 for 150, 12, 6, and 3 patients, respectively. Cadonilimab was administered as first, second, and third line or beyond in 35 (34.3%), 31 (30.4%), and 36 (35.3%) patients, respectively. Treatment regimens included cadonilimab monotherapy (13.7%), combined with chemotherapy (33.3%), chemoradiotherapy (19.6%), anti-angiogenesis therapy (11.8%), chemotherapy and anti-angiogenesis therapy (7.8%), chemoradiotherapy and anti-angiogenesis therapy (10.8%), and surgery plus chemoradiotherapy (2.9%). After a median follow-up of 10.2 months, median PFS and OS were not reached. Among the 93 patients (88.2%) with evaluable efficacy, 8 were CR, 32 were PR, 32 were SD, and 22 were PD. The ORR reached 43.0% and the DCR reached 77.4%. Adverse events were reported by 88.2% of patients, with 31 (30.4%) experiencing grade 3-4 immunotherapy-related adverse effects, mainly decreased white blood cell count(21 patients, 20.6%),, anaemia (6, 5.9%), infection (4, 3.9%), and increased alanine aminotransferase (3, 2.9%). Treatment discontinuation or reduction due to toxicity occurred in 17 patients (16.7%). There were no treatment-related deaths. Conclusions: Cadonilimab demonstrates efficacy and safety for patients with recurrent/metastatic cervical cancer in a real-world setting.
Prognostic analysis of PD-1/CTLA-4 bispecific antibody combined with chemotherapy first-line treatment for recurrent or metastatic cervical cancer: A multicenter real-world study.
Authors: Li Jiwei , Wu Tao , Deng Yuping , Xu Chao , Jiang Yupeng , Zou Wen , Feng Yeqian , Wu Lin , Wang Jingjing 
Published: July 2024

e17520 Background: PD-1/CTLA-4 bispecific antibody, cadonilimab, has shown excellent efficacy in advanced cervical cancer patients who have previously received platinum containing chemotherapy. However, its effectiveness in first-line treatment remains unclear yet. This study aims to evaluate the efficacy, safety, and prognostic biomarker of cadonilimab combined with chemotherapy for the first line treatment of recurrent or metastatic cervical cancer. Methods: Information on patients with recurrent or metastatic cervical cancer who received chemotherapy combined with cadonilimab as first-line treatment at three cancer centers from July 2022 to September 2023 were collected. Patients have not received systemic chemotherapy previously and are not suitable for curative local treatment, received cadonilimab 10mg/kg Q3W for up to 17 cycles + chemotherapy for up to 6 cycles (paclitaxel 135-175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5), ± bevacizumab 10-15 mg/kg. Clinical outcomes were analyzed using the Kaplan–Meier method with log-rank test. RNA-seq was used to analyze differential expressed genes (DEGs) between PR+CR group and PD+SD group. Results: There are 52 patients enrolled, median age 56.5 years (39–87 years). The median follow-up time was 12 months (5–23 months). There were 29 cases of lung metastasis, 7 cases of liver metastasis, 11 cases of bone metastasis, 12 cases of pelvic metastasis, and 11 cases of lymph node metastasis. The median number of cycles of cadonilimab and chemotherapy were 8 and 5, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 91% and 72.5%, respectively. The objective response rate (ORR) was 75%.The expression of PD-L1 and bevacizumab had no effect on prognosis. The most common treatment-related adverse events (TRAEs) were neutropenia (78.2%), anemia (82.7%), thrombocytopenia (51.9%), thyroid dysfunction (50%), nausea and vomiting (88.5%), fatigue (71.2%). Grade 3 or 4 adverse events (AE) were reported in 36.5% patients, mainly hematological toxicity. The most significant differential pathways between PR+CR group and PD+SD group were adhesion, Hippo signaling pathway, NOD like receptor signaling pathway, programmed cell death, and secretory granules. Conclusions: Cadonilimab combined with chemotherapy ± bevacizumab as first-line treatment for recurrent or metastatic cervical cancer was effective and well-tolerant.