bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival outcomes with regular recurrence surveillance following surgical resection in early-stage hepatocellular carcinoma: Insights from a multicenter prospective study.
Authors: Yang Tian , Yao Lan-Qing , Liu Han , Diao Yong-Kang , Wu Yi-Fan , Li Chao , Liang Ying-Jian , Zeng Yong-Yi , Wang Ming-Da , Shen Feng , Lv Guo-Yue 
Published: July 2024

e16259 Background: While surgical resection stands as the primary curative approach for early-stage hepatocellular carcinoma (HCC), the looming risk of recurrence significantly impacts long-term outcomes. This study investigates the influence of regular recurrence surveillance on the long-term prognosis of HCC patients after curative surgical resection. Methods: In this large multicenter observational study, patients who underwent curative resection for early-stage (BCLC stage 0/A) HCC were divided into two cohorts: those adhering to a structured surveillance protocol (regular check-ups every 2-3 months for the first two years, followed by biannual check-ups) and those with irregular or no recurrence surveillance. Key metrics compared between these groups included overall survival (OS), time-to-recurrence (TTR), and post-recurrence survival (PRS). Results: The study encompassed 1,544 patients, with 786 (50.9%) adhering to regular surveillance for postoperative recurrence. Patients under regular surveillance, as opposed to those with irregular/no surveillance, demonstrated a comparable TTR (median: 61.4 vs. 66.2 months, P = 0.161). However, they exhibited significantly improved OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) in cases of recurrence. Multivariable Cox-regression analysis identified regular recurrence surveillance as an independent protective factor, significantly enhancing OS (HR: 0.777; 95% CI: 0.663-0.910; P = 0.002) and PRS (HR: 0.523; 95% CI: 0.428-0.638; P < 0.001). Conclusions: Regular recurrence surveillance markedly improves OS and PRS in patients undergoing surgical resection for early-stage HCC. This study underscores the critical importance of adherence to a structured surveillance regimen in HCC management, potentially enhancing opportunities for subsequent curative interventions and improving long-term survival outcomes. [Table: see text]
Treatment modalities for advanced solid pseudopapillary tumor of the pancreas.
Authors: Yue Mengli , Mao Yize , Yang Qiuxia , Wang Fang , Tang Honggui , Yu Xiaofang , Li Shengping , Wang Fenghua 
Published: July 2024

e16327 Background: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. However, a minority of SPT patients present aggressive behavior and develop recurrent or metastatic diseases. The treatment strategies of advanced SPTs remain unclear. Our study aimed to explore the treatment modalities of aggressive SPTs and the role of endocrine therapy. Methods: The data on clinicopathologic characteristics and treatment of advanced SPT patients from Sun Yat-Sen University Cancer Center and Shen Zhen People's Hospital were collected. The treatment modalities were explored by co-analyzing our local cohort and published literatures. Single sample gene set enrichment analysis (ssGSEA) was used to explore the functional enrichment pathway (GSE43795). Fresh surgical specimens from 10 SPT patients were collected for endocrine drugs sensitive test in vitro by performing tumor histoculture end-point staining computer image analysis (TECIA). Results: A total of 77 advanced SPT patients including 14 cases in our local cohort and 63 cases from published literatures were enrolled. 60 patients received local treatment including cytoreductive surgery, interventional therapy or radiation therapy. 55 patients who had undergone cytoreductive surgery have better outcome compared with others (P = 0.046, HR = 4.12). 31 patients received systemic chemotherapy and 6 patients received targeted therapy. There were 2 patients achieved partial response after chemotherapy. In our local cohort, 5 patients received endocrine therapy with tamoxifen plus megestrol. One patient achieved partial response with duration of response (DOR) of 89 months. 4 patients showed stable disease. ssGSEA for GSE43795 showed that Wnt signaling pathway and its inhibitory pathway-progesterone receptor signaling pathway were simultaneously enriched in SPTs. The results of endocrine drug sensitive test in vitro by TECIA showed response rate of 50% (5/10) in megestrol group, 40% (4/10) in tamoxifen group, and 30% (3/10) in testosterone propionate group. Conclusions: Advanced SPTs did not appear chemosensitive. Cytoreductive surgery may improve survival. Simultaneously enriching Wnt and progesterone receptor signaling pathway may partially explain the low aggressive ability of SPT and their unbalance may lead to the aggressive behavior of SPT. Endocrine therapy with tamoxifen plus megestrol, by enhancing the progesterone signaling pathway, seems to be a promising regimen for advanced SPTs, which is worth to be noted and further studied.
Efficacy and safety of sitagliptin, in combination with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Zhou Tianxing , Wang Xiuchao , Yang Chao , Yu Jun , Hao Jihui 
Published: July 2024

e16329 Background: Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to identify new targets and compounds to overcome chemotherapeutic resistance. Methods: The high-throughput virtual drug screening, molecular docking analysis and organoid biobank-based drug screening were performed to identify the candidates to efficiently overcome chemotherapy resistance. In vitro and in vivo PDOs, PDXs and KPC GEMM models were used to evaluate the effects of the compounds. Spatial single cell RNA-sequence, spatial metabolomics and proteomics were employed to elucidate the mechanism. Additionally, an ongoing open-label, randomized, single-arm, single-center phase 2 investigator-initiated clinical trial (NCT05947825) is investigating the efficacy and safety of the candidate in sensitizing gemcitabine plus nab-paclitaxel (GnP) in previously untreated advanced PDAC patients. Objective tumor responses were assessed according to RECIST1.1 criteria and any adverse events were graded using CTCAE 5.0. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and treatment-emergent adverse events (TEAEs). Results: High-throughput drug screening of chemotherapy-resistant PDOs identified Sitagliptin that could significantly induce the degradation of RRM1/RRM2 in a ubiquitin proteasome-dependent manner and further result in unrestrained pyrimidine biosynthesis and alleviation of replication stress. In vitro and in vivo assays confirmed that Sitagliptin could synergistically enhance the ability of GnP regimen to suppress PDAC progression. In the phase 2 study (NCT05947825), previously untreated advanced PDAC received Sitagliptin, 100mg/qd and gemcitabine (G, 1000mg/m2 )plus nab-paclitaxel (nP, 125 mg/m2 )on Days 1 and 8 in a 21-day cycle. Till February 1, 2024, 12 patients with ECOG 0 to 2 have been enrolled in the study. The primary endpoint has not been reached. Among the 8 evaluable patients, 3 showed partial responses and 5 had stable diseases. The objective response rate (ORR) and disease control rate (DCR) were 37.5% and 100% respectively. There were no instances of treatment-related death in this study. The most common treatment-emergent adverse events (TEAEs) were decreased white blood cells and fatigue. One patient experience skin rash. Conclusions: Sitagliptin could effectively improve efficacy of GnP regimen by suppressing RRM1/RRM2-mediated pyrimidine metabolism. Sitagliptin plus GnP regimen is a feasible regimen with a manageable safety profile. Sitagliptin in combination with GnP regimen shows encouraging antitumor activity in PDAC, meriting continued development. Clinical trial information: NCT05947825 .
Preliminary results from a multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).
Authors: Wen Feng , Tan Ping , Lin Tianhai , Zhang Peng , Shen Yali 
Published: July 2024

e16595 Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting. The preliminary results would be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). 51 patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive MIBC will be included. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Treatment efficacy will be performed by imaging and transurethral resection of tumors after the neoadjuvant treatment. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are disease control rate (DCR), overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Results: Until now, 18 patients were included successfully, with 3 female patients and 15 male patients. And the median age was 64.47 years old. Of them, 7 patients were HER2(2+), and 11 patients were HER2(3+). The clinical stages were T2-4aN0-3M1a. Sixteen patients had the primary efficacy evaluation by now. After the neoadjuvant treatment, 7 patients were T0, 4 patients Tis, 2 patients partial response (PR), 2 patients stable disease (SD) and 1 patient suffered from progress of local disease. Hence the cCR rate was 68.75%, and the DCR was 90.91%. Fourteen patients chose radiotherapy as bladder-sparing therapy and no evidence of tumor in 6 patients who received treatment efficacy after radiotherapy. Two patients received radical cystectomy and pT3N0M0 was achieved for both. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 myositis, grade 1 elevated transaminase and grade 1 hyperthyroidism which led to treatment interruption of tislelizumab. And 10 patients experienced RC48-ADC related toxicities, including grade 1 elevated transaminase, grade 1 erythra and grade 1 paresthesia. No treatment related dose reduction happened. Conclusions: The novel neoadjuvant combination of RC48-ADC and tislelizumab showed promising down stage efficacy in patients with HER2 positive locally advanced MIBC and the toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiECRCT20210564.
Improved detection of homologous recombination deficiency using WES sequencing: Insights into a Chinese pan-cancer cohort.
Authors: Chen Yaru , Suo Peisu , Zhong Jiasheng , Cao Huiya , Ye Haoyang , Chen Shifu , Zhou Yanqing 
Published: July 2024

e17503 Background: Homologous recombination (HR) deficiency has emerged as a novel biomarker for the clinical use of PARP inhibitors in advanced ovarian cancer, and may also be of value in guiding the clinical use of PARP inhibitors and platinum-based drugs in breast cancer, prostate cancer, and other tumors. This significant finding assists in precision medication and prognosis judgments for patients. Methods: This research incorporated a Chinese pan-cancer cohort comprising 1033 patients diagnosed across thirteen cancer types. All matched tumor tissues and peripheral blood samples were processed for the whole exome sequencing. The HRD scoring was conducted with ScarHRD R package with defined parameters for the heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) status. HR deficiency were defined as an HRD-score ≥50 or BRCA1/2 deficient, while HR proficiency were defined as an HRD-score <50 and BRCA1/2 intact. Results: Ovarian cancer demonstrates the highest HRD prevalence at 51.85%, surpassing the BRCA1/2 mutation rate of 20.37%. Breast cancer follows with an HRD rate of 45.45%, yet no BRCA1/2 mutations are detected. Other cancers like pancreatic, gastric, and sarcomas also present notable HRD rates (29.41%, 36.84%, and 29.79%, respectively) without corresponding BRCA1/2 mutations. In contrast, cancers such as urological, lung, intestinal, and neurological tumors exhibit a mismatch between HRD rates and BRCA1/2 mutation presence, few patients with notable BRCA1/2 mutations did not have consisted HR-deficient rate, and vice versa. Conclusions: Analysis HRD-score can help to screen a larger population of PARP inhibitor beneficiaries and provide hope to more patients. In the future we will do more dimensional data analysis statistics on this cohort. [Table: see text]
Clinical efficacy and safety of cadonilimab immunotherapy in patients with advanced cervical cancer: A retrospective study.
Authors: Han Xiuchen , Tan Huaming , Fang Minjie , Wang Minjie , Zhou Yayan , Sheng Xiugui 
Published: July 2024

e17519 Background: For patients with recurrent or metastatic cervical cancer, especially those with negative PD-L1 expression, there is a lack of effective treatment and often indicate poor prognosis. A multicenter retrospective study was conducted to evaluate the safety and antitumor activity of cadonilimab in recurrent or metastatic cervical cancer patients. Methods: Patients with metastatic or recurrent cervical cancer, who underwent treatment of cadonilimab at Shenzhen People’s Hospital and Huazhong University of Science and Technology Union Shenzhen Hospital. All patients received immunotherapy of cadonilimab at a dose of 10mg/kg of body weight with/without the combination of chemotherapy/bevacizumab/ radiotherapy. Cadonilimab were repeated every 3 weeks until disease progression or intolerable toxicity. Antitumor activity and safety were assessed in all patients. Results: Since July 2022 to November 2023. A total of 18 patients (Figo stage IB1-IIIC) with recurrent/metastatic cervical cancer, 3 patients with newly diagnosed advanced cervical cancer (Figo stage IVB stage) were included. With a median follow-up of 7.0 months (IQR 1.9–15.4), the number of treatment cycles for cadonilimab ranged from 3 to 17 cycles, with a median of 7 cycles. 6 patients with PD-L1-positive expression, 5 patients with negative expression, and 10 patients were unknown. 8 patients combined of chemotherapy, 7 patients received cadonilimab monotherapy, 4 patients combined of chemotherapy and bevacizumab, 1 patient combined of bevacizumab, 1 patients combined of chemotherapy, bevacizumab and radiotherapy . 2 patients with newly diagnosed advanced disease and 2 patients with recurrent cervical cancer achieved complete response (CR), 11 patients with achieved partial response(PR) and 1 patients were in stable disease(SD). The objective response rate (ORR) was 71.4% (15 of 21 patients). The ORR of patients with the PD-L1-negative expression was 80% (4 of 5 patients).Grade 3–4 treatment-related adverse events occurred in 7 (33.3%) of 21 patients, the most frequent grade 3-4 adverse events were decreased white blood cell count (3 [14.3%]), decreased platelet count (2 [9.5%]) and anemia (2 [9.5%]). Immune-related AEs (irAEs) were all G1-2, and occurred in 2 (9.5%) patients. None of the patients discontinued treatment because of intolerable toxicity. Conclusions: In this study, cadonilimab containing therapies showed promising results in responses and survival outcomes among patients with metastatic or recurrent cervical cancer and have a favorable safety profile. [Table: see text]
Reflections on the changes in ascites and serum VEGF1 levels before and after intraperitoneal infusion of bevacizumab.
Authors: Du Zhenhua , Xia Yu , Li Xiuqin 
Published: July 2024

e17539 Background: This study analyzes the levels of VEGF1 in ascites and serum before and after intraperitoneal infusion of bevacizumab, aiming to explore the optimal administration route for treating recurrent ovarian cancer accompanied by ascites. Methods: Sixty-seven patients with advanced recurrent ovarian cancer and significant ascites were treated with intraperitoneal infusion of bevacizumab combined with chemotherapy. Under ultrasound guidance, a peritoneal drainage tube was placed, and the volume of ascites was measured before the infusion. The effects of the treatment were assessed by measuring the ascites volume during the 2nd to 3rd treatment (final ascites drainage) and by analyzing and comparing the levels of Vascular Endothelial Growth Factor 1 (VEGF1) in both ascites and serum. Results: The average volumes of ascites before and after treatment were 4229.97 ml and 5.42 ml, respectively (P<0.0001), with an overall response rate (ORR) of 89.6% (60/67). Before and after treatment, the levels of VEGF1 in ascites were 283.86 pg/mL and 18.76 pg/mL, respectively (P<0.0001). Before and after treatment, serum levels of VEGF1 were 80.67 pg/mL and 61.25 pg/mL, respectively (P<0.0001). Before treatment, the level of VEGF1 in ascites at 283.86 pg/mL was significantly higher than in serum, which was 80.67 pg/mL (P<0.0001). The reduction in VEGF1 levels following intraperitoneal infusion was over tenfold greater in serum compared to ascites. When the cutoff value for VEGF1 in ascites was set at 37.12 pg/mL, the sensitivity was 80.28%, and the specificity was 91.55%. Conclusions: The combined treatment of intraperitoneal infusion of bevacizumab with chemotherapy is an effective strategy for controlling ascites in recurrent ovarian cancer. Keywords: Bevacizumab, Intraperitoneal Infusion, Recurrent Ovarian Cancer, Ascites, Vascular Endothelial Growth Factor 1 (VEGF1).
Overall survival in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer (PSROC) treated with olaparib maintenance: Real-world data of the C-PATROL study.
Authors: Marmé Frederik , Hilpert Felix , Welslau Manfred , Grabowski Jacek P. , Schneeweiss Andreas , Hartkopf Andreas D. , Bauerschlag Dirk , Fasching Peter A. , Brandi Christiane , Rehbein John-Kilian , Glowik Regina , Sehouli Jalid 
Published: July 2024

e17542 Background: Maintenance monotherapy with PARP-inhibitor (PARPi), olaparib has previously shown good effectiveness and tolerability in total population of patients with PSROC who were in response to platinum-based chemotherapy (PBC) in the C-PATROL study. Here we present the overall survival (OS) data in different subgroups. Methods: The prospective German non-interventional study C-PATROL (NCT02503436) captured routine clinical data of olaparib maintenance according to label in patients with BRCA-mutated PSROC treated with PBC. The primary endpoint was PFS, relevant secondary endpoints included OS and safety. Data were analyzed by descriptive statistics. Results: Between 10/2015 and 10/2019, 277 patients were enrolled. The ITT set (study selection criteria fulfilled) comprised 267 patients (median age: 60 yrs; ECOG ≤1: 93%; ≥2 relapses: 32%; ≥3 prior PBC: 29%). Median follow-up was 23.5 months (range 0.0–80.5) and median olaparib treatment duration was 13.6 months (0.1–80.9). 10% of patients received olaparib for ≥ 5 years and 8% of patients received further PARPi also as subsequent treatment. Median OS was 35.4 months (95% CI 29.2–49.9). The longest median OS was observed in patients with a complete debulking after the surgery at current relapse, a complete response (CR) to the current PBC and a BRCA2 mutation. Adverse events (AEs) were consistent with the known tolerability profile of olaparib (safety set: n=274; any AE: 95%, AE of CTCAE grade ≥ 3: 40%, olaparib discontinuation due to AE: 11%; most common AE any CTCAE: nausea (46%), fatigue (39%), anaemia (31%), and vomiting (17%); most common AE CTCAE grade ≥ 3: anaemia (14%)). Conclusions: Olaparib is effective and safe in the real-world setting. In olaparib-treated patients with BRCA-mutated PSROC longer OS was observed mainly with respect to resection status after debulking surgery at current relapse, to tumor burden at the therapy start and BRCA mutation type. Our data underline the role of cytoreduction and platinum response in the context of PARPi maintenance therapy. Clinical trial information: NCT02503436 . [Table: see text]
Clinical features and prognostic analysis of 247 patients with ovarian clear cell carcinoma (OCCC) and an exploration of the treatment of recurrent OCCC: A single-center study in China.
Authors: Wu You , Lyu XueYan , Wang Kunyu , Ao Miao , Luo Haixia , Zhang He , Zhang Yuanyuan , Li Bin , Song Yan 
Published: July 2024

e17548 Background: Ovarian clear cell carcinoma (OCCC) is relatively resistant to chemotherapy and has a worse prognosis than other ovary cancer. In this study, we reviewed the case files of OCCC in a single center to find its clinical characteristics and explore the treatment of recurrent cases, and the efficacy of immunotherapy. Methods: From August 2007 to August 2023 247 patients with OCCC were retrospectively involved. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors. The relapse OCCC were divided into four groups based on the different treatment who underwent chemotherapy or chemotherapy combined with surgery, bevacizumab, immune checkpoint inhibitors treatment. Kaplan–Meier curves were utilized to compare OS and DFS/PFS between the groups. Results: (1) 247 patients with OCCC were included, CA125 abnormality (> 35 U/ml) 65.2%, ascites cytology positive 10.1%, and the overall satisfactory reduction of tumor was 92.7%, CR and PR were 93.1 and 6.9%, respectively. 16.2% patients received more than 6 cycles of postoperative chemotherapy.(2)Univariate Cox regression analysis identified ascites (HR=4.012, 95% CI: 1.846 - 8.720, P<0.001), initial treatment effect (HR=2.714, 95% CI: 1.132 - 6.506, P=0.025), and chemotherapy cycles (HR=2.564, 95% CI: 1.402 - 4.689, P=0.002) were identified as independent prognostic factors for OS.(3)The patients who received chemotherapy cycles exceeding 6 cycles had worse prognosis(HR=3.01, 95%CI: 1.70-5.33, P<0.001), the result is the first proposal in our study.(4) Kaplan-Meier survival analysis showed that the OS of the chemotherapy combined with surgery relapse OCCC group was significantly better than the other three groups (HR=0.2732, 95%CI: 10.133-0.559, P=0.001). Subgroup analysis showed that relapse patients with satisfactory tumor reduction had more significant survival benefits(HR=3.86, 95%CI: 0.79-18.93, P=0.096).(5)The PFS of the chemotherapy combined with surgery group was also better than the other three groups (median PFS 25 months vs 8.5 months in chemotherapy vs12 months in chemotherapy combined immunotherapy vs 12 months in chemotherapy combined with bevacizumab). (6)4 patients who tested positive for PD-L1 received immune maintenance therapy after chemotherapy for 6-24months. There has been no recurrence since follow-up. Conclusions: Ascites, initial treatment effect and chemotherapy cycles were identified as independent prognostic factors for OCCC OS, chemotherapy combined with surgery for recurrent OCCC was significantly improving patient prognosis. For patients who achieve CR after initial treatment, if PD-L1 expression is positive, maintenance immunotherapy can be considered, but further studies with large samples are needed.