bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of good outcomes in patients with hepatocellular carcinoma (HCC) treated with transarterial radioembolization (TARE).
Authors: Das Parthib , Paul Samuel , Min Eric , Mittra Arjun , Malalur Pannaga G. , Manne Ashish 
Published: July 2024

e16219 Background: No reliable biomarkers or risk factors guide treatment selection in HCC patients. Management is typically institution-specific, and compliance with the available guidelines is low. Our retrospective review aims to identify HCC patients suitable for TARE. Methods: HCC patients treated with TARE between 1/1/2015 and 8/30/22 at Ohio State University were included in this study. Patient-related information was extracted from chart review. Various risk factors (related to HCC and TARE) were compared between good (GR) and poor (PR) responders (progression-free survival (PFS) ≤ vs. > median (m)), and good (GSv) and poor (PSv) survivors (overall survival (OS) ≤ vs. > m). Chi-square test and logistic regression were performed using JMP Pro 17 (SAS Institute Inc., Cary, NC). Results: Our cohort included 141 patients. The median age was 65 years (range 49-88), 80% were males and 80% were White (16% were African American and 4% were other). The median OS and PFS were 9 months (m) (95% confidence interval [CI], 5-22.5) and 4m (95% CI, 2-9), respectively. Compared to PSv (OS ≤ 9m, N = 71), the GSv group (OS > 9m, N = 70) had a high alcohol history (hx) (64% vs. 44%, p = 0.01); less baseline (BL) encephalopathy (Enc) (21% vs. 37%, p = 0.04) and post-TARE ascites (As) (31% vs. 63%, p = 0.001); were able to receive immune-checkpoint inhibitor (ICI) (44% vs. 6%, p < 0.001) before (6% vs. 1%) or after (39% vs. 10%) TARE. Other key BL features with a trend to significance (p = 0.06-0.08) were less BL cirrhosis (69% vs. 87%) and As (19% vs. 34%), hx of HCC treatment (systemic or local, 43% vs, 28%), and ability to get second TARE (19% vs. 8%). In worse survivors (PFS ≤ 5m, N = 40), post-TARE As (65% vs. 41%, p = 0.008) was significantly higher. Only 2/40 patients were able to get ICI (95% vs. 37%, p = 0.0002) in this group. Compared to PR, the GR group (PFS > 5m, N = 64) had a higher rate of diabetes mellitus (DM) (45% vs. 26%, p = 0.02) and less post-TARE As (34% vs. 58%, p = 0.004). BL and HCC-related factors prominently NOT featured in these comparisons were hepatitis (B or C) or smoking hx and macrovascular invasion. Conclusions: TARE suits patients with hx of alcohol use or DM, no BL Enc, As, or cirrhosis, and failed prior lines. Post-TARE As is poor prognostic markers. ICI use will improve the outcomes.
An open-label, placebo-controlled, randomized phase II trial of camrelizumab combined with or without apatinib or capecitabine in the treatment of previously treated advanced pancreatic cancer.
Authors: Chen Jianhua , Liu Jun , Li Ning , Huang Weiyi , Chen Donghui , Tao Wei , Wang Hongxia 
Published: July 2024

e16324 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types that have essentially no clinical benefit from immune checkpoint inhibitors therapy, combined immunotherapy is expected to solve this dilemma. We conducted a randomized open-label, placebo-controlled phase II trial evaluating the efficacy of camrelizumab combined with apatinib or capecitabine in the treatment of patients with previously treated metastatic PDAC (ChiCTR1900024095). Methods: Eligible patients (n = 30) were randomized 1:1:1 to receive camrelizumab (200 mg q2w) combined with apatinib (250mg qd, d1-28, q4w) or capecitabine (1000 mg/m2, bid d1-14, q3w), or placebo plus capecitabine (1000 mg/m2, bid d1-14, q3w) until disease progression or unacceptable toxicity. Tumor response was assessed every 8 weeks according to RECISTv1.1. Primary endpoints were investigator-assessed 6-month overall survival (OS) rate. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Data cutoff date for the prespecified interim OS and final PFS analysis was Oct 30, 2022. Results: In the primary endpoint analysis, camrelizumab combined treatment showed improved 6-month OS rates, whether in the camrelizumab-apatinib arm (83.3% versus 33.3%, p = 0.1189) or in the camrelizumab-capecitabine arm (100% versus 33.3%, p = 0.0098), compared placebo-capecitabine, respectively. Median PFS was 5.4 months, HR 0.58, [95% confidence interval (CI), 0.21–1.59] in the camrelizumab-apatinib arm , 3.1 months HR 0.98, [95%CI, 0.35–2.77] in the camrelizumab-capecitabine arm , and 2.6 months in the placebo-capecitabine, respectively. The ORR and DCR were 0% and 66.7% in the camrelizumab-apatinib arm, 40% and 50% in the camrelizumab-capecitabine arm, 0% and 44.4% in the placebo-capecitabine, respectively. PR was observed in two patients receiving camrelizumab-capecitabine treatment. The median DoR were 5.3 months in the camrelizumab-apatinib arm, 4.3 months in the camrelizumab-capecitabine arm, and 2.1 months in the placebo-capecitabine arm. Treatment-related adverse event rates were slightly increased in camrelizumab combined arms. Incidences of grade ≥3 treatment-related adverse events were comparable between the three groups (20%、 10% vs 0%), with reactive cutaneous capillary endothelial proliferation (10%) as the most common one in Camrelizumab combinations. Conclusions: Camrelizumab combined treatment showed improved 6-month OS vs conventional capecitabine monotherapy, with a manageable safety profile. These analyses revealed combined immunotherapy could be used as a new option for posterior line treatment in previously treated metastatic PDAC. Clinical trial information: ChiCTR1900024095.
ITGB6 as an inhibitor of T-cell killing via modulation of paracrine TGFβ signaling in pancreatic ductal adenocarcinoma.
Authors: MacDonald William J. , Schwermann Maximilian , Srinivasan Praveen , Tajiknia Vida , El-Deiry Wafik S. 
Published: July 2024

e16334 Background: Immunotherapy has experienced limited success in PDAC, with αPD-1 therapy being approved only in a subset that makes up < 2% of all PDAC cancers. TGFβ is a contributor to T-cell suppression in the PDAC tumor microenvironment. However, the success of blocking TGFβ in preclinical models has failed to translate into the clinic due to the off-target effects of systemic TGFβ blockade. Integrin ITGB6 is an activator of the inert latent TGFβ into the active, immunosuppressive form. Consequently, inhibition of ITGB6 is a potent and targeted therapeutic approach for disrupting TGFβ to overcome T-cell suppression in PDAC. Methods: Analysis of TCGA molecular and survival data was performed to determine the specificity and prognostic value of ITGB6 in PDAC. Subsequently, candidate cell lines were screened for ITGB6 expression using flow cytometry to facilitate an in vitro model. Using a lentiviral system, PDAC cells were transduced with a doxycycline-inducible short hairpin RNA (shRNA) knockdown (KD) of ITGB6. Both KD and control shRNA cell lines were induced with doxycycline and subsequently co-cultured with TALL-104 T-cells. Furthermore, conditioned media was analyzed for secreted active TGFβ levels using a luciferase-based TGFβ reporter cell line. Finally, a clonogenic assay was performed to determine the autocrine effects of TGFβ activation in PDAC. Results: ITGB6 is highly specific to PDAC and also shows upregulation in comparison to normal pancreatic tissue (FC 3.38, p < 0.0001). Capan-2 cells were chosen as a model for high integrin PDAC (Capan-2 99.73% cells ITGB6+, negative control: HCT116WT 0.96% cells ITGB6+). Fluorescent microscopy of the co-culture revealed that the KD of ITGB6 increased T-cell killing over 24 hours (Capan-2 CTRL shRNA 7.71%±3.63 dead vs. Capan-2 ITGB6 shRNA 21.68%±4.57 dead, p < 0.05). Media from ITGB6 KD cells contained significantly decreased TGFβ (+TGFβ: 673000 RLU vs. CTRL: 175500 RLU, p = 0.015). A clonogenic assay of Capan-2 cells treated with active-TGFβ demonstrates that PDAC cells resist the autocrine growth inhibitory effects of TGFβ through loss of SMAD4. TCGA survival data revealed ITGB6 as prognosis marker in PDAC (high ITGB6 median survival 16.79 mos, vs. low ITGB6 21.88 mos, HR = 2.730, p < 0.004). Conclusions: Survival data that clearly demonstrates the poor prognosis of ITGB6 expression, as well as the presently proposed mechanism of immunosuppression, provide ample justification for deploying anti-ITGB6 combination therapies to in vivo studies that facilitate translation of our findings into therapeutic clinical trials.
Pluvicto in the real world setting and timing to PSA50 as a predictive marker of treatment response.
Authors: Maslov Diana Vesselinovitch , New Jacob , Patel Nikunj , Kosty Michael P. , Bhangoo Munveer Singh 
Published: July 2024

e17026 Background: Prostate cancer, the leading cause of cancer mortality in men, has seen notable advances with PSMA-targeted therapies like 177Lu-PSMA-617 (Pluvicto), particularly in the metastatic castrate resistant setting. While prostate specific antigen (PSA) serves as a useful biomarker in newly diagnosed patients or those on androgen deprivation therapy, its efficacy in monitoring patients under PSMA-directed therapy remains unclear. This underscores a critical gap: the absence of established biomarkers for tracking response to these emerging treatments. Such biomarkers are vital for enhancing patient outcomes and evaluating therapeutic efficacy in early-stage trials. Methods: In this real-world, cohort study, we retrospectively followed adult patients with metastatic, castrate-resistant prostate cancer who are treated with Pluvicto at our institution beginning January 1, 2022 through November 2023. We assessed several potential biomarkers of response temporally throughout the treatment duration of Pluvicto, including serial blood counts, chemistry profiles, PSA levels, BMI, as well as their historical treatment patterns and demographics. All patients were heavily pre-treated prior to receiving Pluvicto. By using logistic regression, we identify factors associated with treatment response. Results: In our study, 21 patients qualified for enrolment. These patients received a median of 6 treatments prior to Pluvicto. Among them, 8 (38.1%) demonstrated at least PSA50 and showed response post-treatment. Of these, 6 (75%) completed all six Pluvicto treatments, while 2 (25%) are currently undergoing treatment. Remarkably, 7 of the 8 responders (87.5%) achieved a PSA50 response after two Pluvicto doses, with all 8 (100%) reaching this marker by the third dose. Furthermore, 6 of these 8 patients (75%) exhibited a PSA90 response after the fourth dose, though 2 patients (25%) did not attain PSA90. Conclusions: Our real-world study at Scripps Clinic provides valuable insights into the efficacy of Pluvicto in treating metastatic, castrate-resistant prostate cancer. Out of 21 patients treated with Pluvicto, 38.1% exhibited a significant PSA decrease during the treatment course. Notably, 87.5% of responders achieved PSA50 before their third dose, and all responders reached this benchmark prior to their fourth dose. These findings are crucial, especially as clinical trials are exploring Pluvicto's application in earlier treatment stages. Additionally, the use of PSA50 as a biomarker could guide clinicians in timely decision-making, allowing for quicker intervention and therapy adjustments, thus potentially mitigating disease progression. Updated data to be presented.
Evaluation of malignant potential based on infection with high-risk human papillomaviruses 16, 52, and 58 in the uterine cervix.
Authors: Lee Seung-Mi , Lee Hyun-Jung , Lee Juhun 
Published: July 2024

e17511 Background: The high-risk human papilloma virus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. Generally, gynecologists recommend medical interventions for patients diagnosed with HSIL or higher. Previous studies have evaluated genotype-specific risk for carcinogenesis. However, the genotype-specific risk remains still unclear due to some limitations of those studies. This study aimed to evaluate the malignant potential of the three most prevalent HR-HPVs in Korea. Methods: Patients who underwent uterine cervical conization were included. They had received HPV test within a year before the surgery and those exhibiting concurrent multiple infections with HR-HPVs were excluded. Of single infections with HR-HPV, the three most prevalent HR-HPVs were included to analyze. To evaluate their malignant potential, CIS+, including carcinoma in situ (CIS) and invasive carcinoma, was categorized in each HR-HPV group. The ratios of pathologic diagnoses and odds ratios for malignant potential were evaluated between the three most prevalent HR-HPVs. Results: Totally 230 patients were found to have a single infection with HR-HPV16, HR-HPV52, or HR-HPV58. Of the included patients, 119 (51.7%), 60 (26.1%), and 51 (22.8%) were noted to be infected with HR-HPV genotypes 16, 52, and 58, respectively. CIS was diagnosed in 59 (49.6%), 27 (45.0%), and 25 (49.0%) patients in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.839). Invasive carcinoma, regardless of histology such as squamous cell carcinoma or adenocarcinoma, was diagnosed in 8 (6.7%), 1 (1.7%), and 1 (2.0%) patient in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.187). The CIS+ ratio was not significantly different among the HPV16, HPV52, and HPV58 single infection groups (67 [56.3%] vs. 28 [46.7%] vs. 26 [60.0%], [ p = 0.460]). Conclusions: Among the Korean women with single HR-HPV infection, HPV16, HPV52, and HPV58 were the three most common genotypes, in descending order. Although HPV16 was the most prevalent among the three, its malignant potential was not significantly different from those of HPV52 and HPV58 in the uterine cervix. This result supports the need for a nine-valent vaccine against HR-HPVs, covering HPV52, HPV58, and HPV16.
A study of risk factors and clinico-pathological profile of patients with cervical cancer at BPKIHS: A descriptive cross-sectional study.
Authors: Shrestha Ramesh 
Published: July 2024

e17515 Background: Cervical cancer is the cancer with highest incidence and mortality among females in Nepal according to GLOBOCAN data 2020. The aims of this study was to evaluate the risk factors and clinico-pathological profile of patients with cervical cancer attending Department of Gynaecology, BPKIHS, Dharan, Nepal. Methods: It was a descriptive cross-sectional study conducted from April, 2019 to February, 2022 among seventy-nine patients with histological diagnosis of cervical cancer after ethical approval. Results: The mean age of these patients was 54.99±12.81 years. The commonest presenting symptom was postmenopausal bleeding (65.8%) and the commonest histological type was squamous cell carcinoma (87.3%). The commonly associated risk factors among them were illiteracy (88.6%), poor local hygiene (78.5%), postmenopausal status (72.2%) and poor socio-economic status (41.8%). The mean age at marriage and first pregnancy were 18.45 (SD=2.32) years and 19.47 (SD=2.51) years respectively. More than one-fourth (29.1%) of the patients had more than or equal to 5 children. Only three (3.8%) patients had undergone cervical cancer screening once in their lifetime.Most of them (n=66; 83.5%) had locally advanced disease at diagnosis. Altogether, sixty-seven (84.8%) patients were referred outside for radiation treatment. Among the surgically treated patients, twelve (63.2%) patients subsequently required dual treatment. Conclusions: Illiteracy, poor hygiene, low socio-economic status, patient’s delays, poor screening programmes, multiparity, early age at marriage and first child birth etc. are the factors requiring major focus to reduce the burden of cervical cancer in developing countries like Nepal.
Real-world data of a regimen containing zimberelimab in the treatment of recurrent and metastatic cervical cancer.
Authors: Tian Qiuhong , Xu Qin , Li Fan , Huang Jin , Liu Jing , Zang Lele , Ting Li , He Lianxiang , Yang Wenhan 
Published: July 2024

e17521 Background: Cervical cancer is the malignant tumor in women. Zimberelimab is approved by NMPA for PD-L1 positive recurrent and metastatic cervical cancer. However, no real-world data of zimberelimab in recurrent and metastatic cervical cancer have been reported before. Methods: From August 2021 to March 2023, we retrospectively collected patient data at the First Affiliated Hospital of Nanchang University and Fujian Cancer Hospital. Patients with advanced or recurrent cervical cancer who had been pathologically diagnosed were eligible, regardless of whether they had squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma and PD-L1 status. All patients were treated with regimen containing zimberelimab. Date of brith, previous medical history, tumor stage at first diagnosis, metastatic sites, pathological type, HPV infection and PD-L1 expression status, and treatment regimen containing zimberelimab will be recorded. The primary endpoint was objective response rate and disease control rate assessed by RECIST1.1. The study has been approved by the First Affiliated Hospital of Nanchang University Ethics (No 317). (ChiCTR2300078205). Results: A total of 34 patients were eligible for evaluations of efficacy. 21 from the First Affiliated Hospital of Nanchang University and 13 from the Fujian Cancer Hospital. The median age was 53.23 years (range, 37–66). The ECOG PS was 1 for 23 cases (67.65%), 2 for 10 cases (29.41%).3 for 1 case (2.94%). Squamous cell carcinoma (28,82.35%) was the most common pathological subtype, and the most metastatic site were lymph node (26,76.47%), lung (10,29.41%), bone (6,17.65%), liver (1,2.94%), vulva (1,2.94%), peritoneal (1,2.94%) and bladder (1,2.94%). 32(94.12%) and 30(88.24%) patients have not test for PD-L1 statue or HPV infection. The best overall response of each patient was recorded to evaluate the efficacy. The objective response rate (ORR) in 34 patients were 52.94%, and the disease control rate (DCR) were 97.06%. And 25 patients had previously had ≥1 chemotherapy, and they was treated with a zimberelimab-based combination regimen. The ORR and DCR for these individuals were 52% and 96%, respectively. Conclusions: This is the first report of real-world data on zimberelimab, and zimberelimab combination therapy demonstrated quite good efficacy in patients with recurrence and metastatic cervical cancer who had previously received chemotherapy. Clinical trial information: ChiCTR2300078205. [Table: see text]
Patterns of pembrolizumab use for recurrent cervical cancer.
Authors: Huang Yongmei , Yoh Katherine , Szamreta Elizabeth A. , Xu Xiao , Hershman Dawn L. , Wright Jason Dennis 
Published: July 2024

e17528 Background: Pembrolizumab was approved for treatment of recurrent or metastatic cervical cancer (CC) as a single agent after chemotherapy in 2018 and in combination with chemotherapy in 2021, but little is known about how it has been actually used in clinical care. We examined real-world use of pembrolizumab for recurrent CC. Methods: The Merative MarketScan Research Databases were used to identify newly diagnosed CC patients who underwent primary hysterectomy or radiation between 2017-2022. Utilization of systemic therapy was assessed at the time of primary/adjuvant therapy and at first recurrence. Primary/adjuvant chemotherapy was defined as the use of chemotherapy within 4 months of the first cancer claim. First-line (1L) systemic therapy for recurrence was defined as the introduction of a new agent after a gap of > 3 months for patients who received adjuvant/primary chemotherapy or after 4 months from primary hysterectomy or radiation. Treatment for recurrence was classified as platinum alone, platinum-based combination therapy and non-platinum therapy. The use of targeted therapy (bevacizumab) and immunotherapy (pembrolizumab, nivolumab) was noted. Patterns and duration of use of each agent are described. Results: A total of 2727 patients were identified, including 1259 (46.2%) who underwent primary hysterectomy and 1468 (53.8%) treated with primary radiotherapy. Chemotherapy for recurrent CC was initiated in 339 patients (12.4%). Treatment for recurrence was noted in 9.7% of those treated initially with hysterectomy and in 14.8% of those with primary radiotherapy. Among patients treated for recurrence, 24.8% received platinum alone, 52.5% received a platinum-based combination, and 22.7% received non-platinum regimens. A total of 41 patients (12.1%) received pembrolizumab after recurrence, including 7.1% who received pembrolizumab alone, 2.1% who received pembrolizumab in combination with platinum, and 2.9% who received pembrolizumab with non-platinum therapy. Pembrolizumab was used after recurrence in 15.7% of patients who received chemotherapy during primary therapy compared to 7.1% of those who did not receive primary chemotherapy. Use of pembrolizumab was 11.4% in 2018, 17.6% in 2019, 14.0% in 2020, 8.8% in 2021, and 11.8% in 2022. The median duration of 1L chemotherapy for recurrence was 2.3 months (IQR, 1.0-5.8) overall, and 4.3 months (IQR, 2.4, 9.8) for patients treated with pembrolizumab. Patients who had not received primary/adjuvant chemotherapy had a longer duration of treatment with pembrolizumab than those who had received upfront chemotherapy, median 7.5 (IQR 3.9-9.8) versus 4.0 (IQR 2.2-11.0) months, respectively. Conclusions: Platinum-based chemotherapy remains the predominant therapy for recurrent CC. Pembrolizumab use is increasing for patients with recurrent cervical cancer. Longer follow-up is necessary to further evaluate its post-approval usage.
Molecular characteristics of non-human papillomavirus driven cervical adenocarcinoma and adenosquamous carcinoma.
Authors: Lai Chyong-Huey , Lin Chiao-Yun , Wu Ren-Chin , Chao Angel 
Published: July 2024

e17532 Background: Cervical cancer is the fourth most common malignancy in women worldwide. Although infection from human papillomavirus (HPV) has been the major cause of cervical cancer, about 3-8% of cervical cancer cases are HPV-negative. Clinical data showed that patients with HPV-negative cervical cancer had significantly lower DFS than those with HPV-positive cervical cancer. The detection of HPV DNA tends to be lower in adenosquamous carcinoma (AC/ASC) than in squamous cell carcinoma. Because the mechanism of HPV-negative cervical cancer development is unclear, this study aims to find the pattern of differential gene expression in HPV-negative AC/ASC and verify the underlying potential mechanism. Methods: In this study, we aimed to exam the differential gene expression profiling by exome-capture RNA sequencing on formalin-fixed, paraffin-embedded tumor tissue of prospectively enrolled cervical AC/ASC patients (HPV-negative: HPV-positive: 1:1) and validate the selected biomarkers on the remaining (unmatched; n = 110) prospective cohort and the 274 retrospective cohort patients. Subsequently, dysregulated differentially expressed genes specifically existed in HPV-negative cervical AC/ASC tissues and HPV-negative cell lines were validated by Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical staining (IHC staining). Results: Exome-capture RNA sequencing on HPV-negative and age/grade matched HPV-positive AC/ASC (10:6) for discovery initially. We found differentially activated WNT pathway from HPV positive/negative AC/ASC in the prospective cohort. In the preliminary results of 28 prospective cohort patients, SOX17 and MMP7 highly expressed genes in HPV-negative (n = 13) then the HPV-positive (n = 11) cervical AC/ASC by IHC staining (p = 0.1029 and p = 0.0306, respectively). Moreover, plasma MMP7 levels were upregulated in HPV-negative AC/ASC (n = 10) compared with HPV-positive AC/ASC (n = 17) (p = 0.0086) by ELISA analysis in the prospective cohort. Conclusions: Further studies and more analyses will be continued to investigate the effects of changes in the expression of SOX17 and MMP7 related mechanisms, and targeting WNT/SOX17/MMP7 pathways specifically associated with HPV-negative AC/ASC to provide new insights into the early screening and effective treatment of HPV-negative AC/ASC.