bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world characteristics and treatment pattern of patients with newly diagnosed endometrial cancer in China.
Authors: Yin Aijun , Wang Dong , Luo Yanlin , An Ruifang , Yao Shuzhong , Shen Yufei , Sun Li , Lei Cuirong , Tian Yan , Wang Li , Zhong Dan , Xu Manman , Jiang Yuanyuan , Zhang Min , Zhang Binqi , Mao Huirong , Dong Fengshi , Zhang Yu , Kong Beihua 
Published: June 2023

e17613 Background: Endometrial cancer (EC) is the second most common gynecologic cancer in China with an increasing incidence. Currently, there is no comprehensive profile of EC patients in China. This real-world multicenter retrospective study aimed to depict the characteristics and treatment patterns in newly diagnosed EC patients in China. Methods: Medical records of newly diagnosed EC at 8 hospitals between January 1, 2015 and December 31, 2019 were retrospectively reviewed. The demographic and clinical characteristics at diagnosis as well as the treatment received within 6 months after diagnosis were collected. Results: A total of 1397 patients were enrolled in the study. The average age was 53.5 years. The number of patients (n=1256) classified as stage I, II, III, and IV was 885 (70.5%), 141 (11.2%), 207 (16.5%) and 23 (1.8%), respectively. The number of patients (n=1340) presented with low-grade (G1-2) and high-grade (G3) tumors was 924 (74.0%) and 324 (26.0%), respectively. Invasion of lymphovascular space was detected in 237 (17.0%) out of 1397 patients. Among 1389 patients with pathological data, pure endometrioid carcinoma (90.3%) and serous carcinoma (5.1%) accounted for the majority of pathological types. Estrogen receptor (ER) expression was positive in 91.0% (977/1074) of patients and progesterone-receptor (PR) expression was positive in 85.2% (904/1061) of patients. Mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) was identified in 26.6% (107/402) of patients. Among 1393 patients with treatment information, surgery was performed in 99.6% of patients and 66.9% received adjuvant treatment following surgery according to clinicopathological risk factors. The percentage of patients receiving adjuvant chemotherapy, adjuvant radiotherapy, and adjuvant chemoradiotherapy was 36.7%, 7.3%, and 22.0%, respectively. Among 306 patients who received chemoradiotherapy, 47.1% underwent concurrent chemoradiotherapy, 31.0% underwent sandwich chemoradiotherapy, and 21.9% underwent sequential chemoradiotherapy. Conclusions: To date, this is the first real-world study with largest sample size of EC patients in China. EC is frequently diagnosed at early 50s in Chinese patients, which is at a younger age compared with European and American population. Newly diagnosed EC patients in China are primarily treated with surgery. Chemotherapy and radiotherapy remain the main adjuvant treatment after surgery. MSI-H/dMMR patients accounted for about 1/4 of newly diagnosed patients, for whom immunotherapy may open up better prognosis in the future.
Immunohistochemical expression of ER and p53 as predictive biomarkers of immunotherapy in endometrial cancer.
Authors: Liontos Michael , Papanota Aristea-Maria , Svarna Anna , Pergialiotis Vasileios , Fiste Oraianthi , Markellos Christos , Kunadis Elena , Potiri Eirini , Andrikopoulou Angeliki , Papatheodoridi Alkistis , Koutsoukos Konstantinos , Kaparelou Maria , Goula Kalliroi , Pavlakis Kitty , Thomakos Nikolaos , Haidopoulos Dimitrios , Rodolakis Alexandros , Zagouri Flora , Dimopoulos Meletios A. 
Published: June 2023

e17626 Background: Immune Checkpoint Inhibitors (ICIs), either as monotherapy or in combination with tyrosine kinase inhibitors (TKIs), were recently incorporated into the therapeutic guidelines for recurrent/metastatic endometrial cancer (EC). Microsatellite Instability (MSI) is the only biomarker to guide treatment. We evaluated the predictive significance of Estrogen Receptor (ER) and p53 expression. Methods: Medical charts of EC patients that received ICIs in our institution for advanced/metastatic disease were retrospectively reviewed. TP53 and ER expression were determined by immunohistochemistry. Survival analysis was performed using IBM SPSS statistics v.25. Results: Thirty-two patients were included in our analysis. The median age was 63.1 years (25th-75th percentile: 57.6 – 69.6). 62.5% of the patients had endometrioid histology, 21.9% serous histology and 15.6% of them displayed other histology. 46.9% of the patients had grade 1-2 tumors and 53.1% grade 3 tumors. 21.9% of them were diagnosed with stage 1-2 disease, while 78.1% presented with stage 3 disease. 62.5% received 0-1 prior lines of treatment and 37.5% of them received more than 2 prior lines. Molecular characteristics are presented in the table. All MSI-High patients received anti-PD1 monotherapy with a median PFS of 11.9 months (95% CI:2.3-21.5). Microsatellite Stable (MSS) patients received pembrolizumab-lenvatinib combination with median PFS 7.54 months (95% CI:2.6-11.5). ER positivity was associated with significant PFS benefit in both the ICI monotherapy group (11.9 vs. 0.63 months, p=0.061) and the group that received ICI/TKI combination (11.3 vs. 1.75 months, p=0.001). Analogous benefit was noted in the Overall Survival post start of IO or IO/TKI treatment (9.8 vs 0.6 months in MSI-high patients and 20.6 vs 5.9 months in MSS patients). ER-positivity remained an independent predictive factor favoring PFS in the Multivariate Cox regression analysis when adjusting for immunotherapy type, histology, and previous lines of therapy (HR=0.216, p=0.013). Conclusions: ER expression proved to be an independent prognostic factor regarding PFS in our cohort of patients. Further studies are needed to investigate the role of ER as a predictive biomarker for immunotherapy in EC. [Table: see text]
The utilization of lenvatinib with pembrolizumab for the treatment of recurrent endometrial cancer.
Authors: Barbi Mali , Lee Chung-Shien , Rahman Husneara , Cheng Kit , Jean Lee , John Veena S. 
Published: June 2023

e17627 Background: The landscape for the treatment of microsatellite-stable-recurrent endometrial cancer has changed with the published results of the KEYNOTE-775, demonstrating an overall response rate of 37.2% with Pembrolizumab and Lenvatinib 20 mg. However, recent retrospective studies have suggested that a lower dose of Lenvatinib may be safer and equally efficacious. We aimed to retrospectively review our institutional data to compare the efficacy and toxicity of Lenvatinib at a low (≤10 mg) vs. high (>10 mg) dose. Methods: Retrospective review of patients with recurrent endometrial cancer who received ≥ 3 cycles of Pembrolizumab with Lenvatinib. A Univariate analysis was used to estimate the 1-year progression-free survival (PFS) and overall survival (OS), and a Multivariate Cox PH regression model was used to estimate the hazard ratio (HR) with a 95% confidence interval (CI) and p<0.05. Results: 77 patients were included in this analysis, the median age and BMI were 70 years and 28.5 kg/m2, respectively (Table 1). Most tumors were PDL-1<1% (67.2%) and were microsatellite stable (95%). 4 patients had MSI-H. Most patients started at a lower dose (66%, median of 10 mg), and 34% of patients started at a higher dose (n=26, median of 14 mg). The most common dose was 10 mg (41%, n=32) and 13% of patients received 20 mg (n=10). In the lower dose group, 71% had ECOG 0-1 vs. 77% in the higher dose, and were more likely to have > 2 lines of treatment (45% vs. 22%). The median time to interruption was 41 vs. 51 days respectively. The PFS and OS were not statically different (Table 1). Multivariate analysis showed a significantly higher HR in the lower dose group (2.5 [CI 1.12-5.56], p=0.025). Conclusions: TheFDA-recommended dose of Lenvatinib of 20 mg is perceived to be difficult to tolerate and patients are often started on a lower dose. In this study, we observed that the time to interruption was longer in the higher dose than in the lower dose group. Though we failed to detect a significant differences in PFS/OS, when adjusted for age, we observed a significantly higher HR of progression or death in the lower dose group. Possible explanations for our observations are that patients who received a lower dose were older and frailer. Our findings call to question the common practice of starting Lenvatinib at a low dose. Further analysis is warranted to delineate the required dose that is both efficacious and safe. [Table: see text]
The distribution of HPV subtype in vulvar intraepithelial neoplasia and the association with recurrent VIN and vulva cancer in Taiwan.
Authors: Liao MIN-Jie , Lai Chyong-Huey 
Published: June 2023

e17635 Background: Vulvar intraepithelial neoplasia (VIN) is a precursor lesion of vulvar cancer. Human papillomavirus (HPV) is causative for part of VIN lesions. This retrospective study aimed to investigate HPV distribution in patients with vulvar intraepithelial neoplasia (VIN) and the factor associated with the recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+), high-grade vaginal intraepithelial neoplasia (VAIN) , cervical intraepithelial neoplasia(CIN) or progression to vulvar cancer. Methods: We retrospectively analyzed patients who diagnosed as vulvar squamous intraepithelial lesions between 1990 and 2014 in our institution. All the diagnoses and classifications were confirmed by two pathologists in 2015 ISSVD terminology. HPV DNA was extracted from formalin-fixed and paraffin-embedded samples. SPF1/GP6+ polymerase chain reaction (PCR) followed by HPV Blot and E6 type-specific PCR were performed. Results: Ninety-eight VIN patients were included in our analysis. Ninety-three percent were positive for HPV and HPV16 (43.9%), HPV6 (11.38%), HPV11 (8.94%), and HPV58 (4.88%) were the most prevalent types. Patients with positive HPV were diagnosed younger than those with negative results (43.0 years vs. 61.1 years, P = 0.049). In 15 patients who with recurrent VIN (n = 11) or progression to vulvar cancer (n = 4), had positive HPV. All 4 patients who had progression to cancer were positive for HPV16 in their initial VINs. High risk type HPV infection, positive HPV16, and positive alpha-9 types are significant risk factors for recurrent VIN and progression to cancer. Conclusions: Positive HPV was detected in 92.8% of VINs and was related to younger age at diagnosis. HPV16 was the most prevalent type and was significantly related to recurrence/ progression. Other significant risk factors for recurrent VIN or progression to cancer were high-risk HPV and alpha-9 types. Closely monitor of those patients with risk factors was indicated for early detection and treatment of recurrent VIN and vulvar cancer.
Social determinants of survival in head and neck cancer.
Authors: Kennedy Kim Robyn , Gibson Daren Joseph , Flukes Stephanie , Spalding Lisa Jane , Diwakarla Chandra Sai , Redfern Andrew David 
Published: June 2023

e18008 Background: Social demographics and health inequalities are associated with adverse outcomes in cancer. Methods: We conducted a retrospective review of 320 Head and Neck Cancer patients between 2013-2021 in a tertiary centre in Western Australia. We matched 80 Aboriginal patients with 240 non-Aboriginal patients by disease site, histology, age, and rurality. Data collected included tumour site, patient demographics, treatments, recurrences, and survival outcomes. An initial univariate analysis was performed using Chi-Square and Kaplan Meier analyses; however a multivariate analysis will be conducted for subsequent publication. Results: Median follow-up was 2.6 years (range 16 days to 9 years). 44% of patients underwent curative intent radiotherapy or chemoradiotherapy, 38% had surgery (+/- adjuvant therapies), 9% had palliative treatments, and 9% had best supportive care. Overall survival (OS) using Kaplan-Meier was inferior for Aboriginal patients compared with non-Aboriginal patients; 1 year survival (YS) 59% vs 85% and 5YS 32% vs 60% (p < 0.00001). Of patients receiving curative intent treatment, relapse occurred in 47% of Aboriginal patients compared with 29% of non-Aboriginal patients (p = 0.01), with inferior progression-free survival (PFS) 1 yr PFS 71% vs 81% and 5yr PFS 52% vs 72%, p = 0.006. 2YS was highest in regional patients (77%), followed by metropolitan (68%), and lowest in remote patients (61%), p = 0.04. 21% of remote patients opted for palliative treatment despite curative treatment being recommended, compared with 3% of regional and 4% of metropolitan patients. Amongst patients receiving curative treatment (81%), metropolitan patients had the highest risk of relapse (42%), compared with remote (31%) and regional (23%), p = 0.02. Despite this, in the same group of treated patients, remote patients had the lowest survival (2YS 88% regional, 80% metropolitan, 75% remote, p = 0.04). Ever smokers had lower 1YS (91% vs 76%, p = 0.03), a higher risk of relapse (28% vs 21%, p = 0.01), and a lower likelihood of disease-free survival (53% vs 74%, p = 0.01) compared to never smokers. Alcohol excess was associated with inferior 1YS (84% 0-4 std/d, 85% 5-10 std/d, 57% > 10 std/d, p = 0.00004), and a higher risk of relapse (19% for non-drinkers, 35% 1-4 std/d, 27% 5-10 std/d, and 64% for > 10 std/d, p = 0.00007). Marital stability was associated with improved 1YS (88% married, 78% widowed, 78% de facto, 76% divorced, 65% single, p = 0.004). Single patients had the lowest likelihood of disease-free survival (42%), followed by divorced (50%), de facto (50%), and widowed (65%). Married patients had the best disease-free survival (66%), p = 0.002. Non-English speaking status was associated with inferior 1YS (79% vs 40%, p = 0.006). Conclusions: Aboriginal status, rurality, smoking, high alcohol consumption, single or divorced individuals, and non-English speaking were all associated with poorer outcomes.
Chemotherapy combined with anlotinib, toripalimab and stereotactic radiotherapy in oligo-metastatic nasopharyngeal carcinoma: A prospective, multicenter phase II clinical study.
Authors: Yang Dong , Hu Xueying , Ruan Lin , Yang Zhendong , Zhang Tingting , Qin Yutao , Liu Kang , Liang Fangfang , Qin Yating , Huang Heqing , Li Pian , Du Guobo , Lu Ying , Han Yaqian , Wang Rensheng , Kang Min 
Published: June 2023

e18011 Background: Distant metastasis is the main cause of nasopharyngeal carcinoma (NPC) related death while there are few treatment options for it. How to further improve the survival of NPC patients with distant metastases is an urgent problem to be solved in clinical practice. This study investigated the efficacy and safety of chemotherapy in combination with anlotinib (a multi-target tyrosine kinase inhibitor), toripalimab, and stereotactic radiotherapy(SBRT) in treatment of metastatic NPC. Methods: This is a prospective, multi-centered, single-arm, phase II trial (ChiECRCT20210147). Patients with histologically confirmed non-keratinous carcinoma and post-treatment metastatic NPC (stage IVb, AJCC 8th) who had no local recurrence and received no systemic antitumor therapy for metastatic lesions previously were enrolled. No more than 5 metastatic lesions (metastatic sites include lung, liver, bone, etc.), and with at least one measurable target lesion according to RECIST1.1. Other inclusion criteria included 18-65 years old and ECOG 0-1. All patients received gemcitabine (1000 mg/m2, ivgtt, d1/8), cisplatin (80 mg/m2, ivgtt, d1), toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 6 cycles, then followed by toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 11 cycles. The SBRT was initiated after 2 cycles of chemotherapy (bone GTV 30-45Gy/3-5f, liver and lung GTV 45-60Gy/4-6f). The primary endpoint was objective response rate (ORR). Here we report the results of a preliminary analysis. Results: Between January 2022 and January 2023, a total of 19 patients were enrolled (13 males and 6 females), the median age was 46 years old. At the data cutoff date on January 31, 2023, 15 patients were eligible for the evaluation of tumor response with metastatic lesions. 100% of the patients (15 of 15) had a response and the confirmed ORR was 100% (complete response, n = 4; partial response, n = 11) for metastatic lesions. The most common treatment-related adverse events (TRAE) of any grade were leukopenia (15 of 15,100%), anaemia(13 of 15, 93.3%), decreased appetite (10 of 15, 66.7%), hypothyroidism (6 of 15, 40.0%), rash(5 of 15, 33.3%) and pneumonitis (5 of 15, 33.3%). Grade 3-4 TRAE included leukopenia (3 of 15, 20.0%) and no fatal adverse events occurred. Conclusions: This preliminary analysis indicated that chemotherapy combined with anlotinib, toripalimab, and stereotactic radiotherapy had promising efficacy and favorable tolerance as treatment of oligo-metastatic NPC. Clinical trial information: ChiECRCT20210147 .
Comparison of first-line treatments for recurrent or metastatic nasopharyngeal carcinoma based on phase 3 randomized clinical trials.
Authors: Xiong Wei , Zhu Lixiu , Xu Guoqiang , Xia Yaoxiong , Wang Hu , Xu Tianrui , Li Xin , Xue Yongyuan , Li Zhengfei 
Published: June 2023

e18012 Background: Guidelines recommend platinum-based chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients. There are a variety of available combination treatment options, however, there is lack of research evaluating their advantages and disadvantages. Therefore, this study aims to compare the efficacy and adverse events (AEs) of the first-line treatment for R/M NPC. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for phase 3 randomized clinical trials (RCTs) in which two first-line treatments for R/M NPC were compared. Among the included trials, progression-free survival (PFS) and overall survival (OS) were calculated using the hazard ratio (HR) and 95% Bayesian confidence interval (95% CrI), while the odds ratio (OR) and 95% CrI were used to evaluate the incidence of severe AEs. The cumulative ranking plot and surface under the cumulative ranking curve (SUCRA) were used to evaluate the rank probability of each regimen. Results: Three trials involving 4 total regimens were included. In terms of PFS, toripalimab plus gemcitabine plus cisplatin (GP) (HR: 0.28; 95% CrI: 0.081-0.98) and camrelizumab plus GP (HR: 0.28; 95% CrI: 0.079-0.96) were significantly superior to fluorouracil plus platinum (PF). In the rank analysis, camrelizumab plus GP was most likely to be the best regimen (SUCRA = 0.81), followed by toripalimab plus GP (SUCRA = 0.80). There was no significant difference among these treatments in terms of OS or AEs. Conclusions: This is the first network meta-analysis comparing the pros and cons of first-line regimens for R/M NPC based on phase 3 randomized clinical trials. Our research showed that toripalimab/camrelizumab plus GP was found to be the most effective treatment regimens for the first-line treatment for R/M NPC in terms of PFS.
Evaluating the efficacy and safety of pembrolizumab monotherapy or in combination with standard chemotherapy in the first-line treatment of locally recurrent head and neck squamous cell carcinoma in different TP53 and PI3K statuses.
Authors: Zhang Shurong , Zhang Boyao , Li Xinyu , Dang Shoutao , Zhao Jingyang 
Published: June 2023

e18014 Background: Pembrolizumab (pembro)-based therapy is currently widely used in recurrent/metastatic head and neck squamous-cell carcinoma (R/M HNSCC). The study will explore the association between different TP53 and PI3K statuses and survival in locally recurrent HNSCC. Methods: This is a prospective, single-center study analyzing patients with locally recurrent HNSCC and prior platinum-based chemotherapy for at least 6 months without progression. Patients received pembro monotherapy (200mg) or pembro plus standard chemotherapy (PF, TP, P, G, GP; paclitaxel 175mg/m2, cisplatin 100 mg/m2, 5-fluorouracil 1000 mg/m2 per day for 4 consecutive days, Gemcitabine 1000mg/m2 day 1 and day 8) every 21-day for 6 cycles and followed by pembro maintenance therapy until progression or unacceptable toxicity or 35 cycles, whichever occurred first. Patient’s response to the therapy was evaluated using RECIST 1.1. Primary endpoint was PFSITT,PFSTP53mut,PFSTP53wt, PFSPI3Kmut/amp and PFSPI3Kwt. Secondary endpoint was ORR, DCR and OS of ITT patients and combination group. Results: From January 8, 2020 until September 20 2022, 20 patients were enrolled. Median age was 56 (range 47-73). Baseline HPV positive (1,5%), HPV negative (12,60%) and HPV unknow (7,35%). TP53mut (9,45%) and TP53wt (7,35%), TP53 unknow (4,20%). PI3Kmut/amp (2,10%) and PI3Kwt (11,55%), PI3K unknow (7,35%). CPS≥20 (3,15%), CPS 1-19 (9,45%), CPS unknow (8,40%). Primary region showed that 1 patients (5%) in the oral cavity, 2 (10%) in the oropharynx, 7 patients (35%) in the larynx, 4 (20%) in the hypopharynx, 2 (10%) in the sins, 1 (5%) in the epithelial-myoepithelial and 3 (15%) in the unknown primary site. There were 16 patients (80%) with only local recurrent disease, 4 (20%) with local disease combined with distant diseases at enrollment. Median follow-up was 2 years. Adverse reactions are overall controllable (Table), but who one died with grade 4 cardiotoxicity The mPFSITT was 4.9 months, PFSmono was 4 months and PFScombination was 4.93 months (p=0.89). The mPFSITT+TP53mut was 5.1 months, mPFSITT+TP53wt was 4.6 months (p=0.63). mPFSITT+PI3Kmut/amp was 7.2 months and mPFSITT+PI3Kwt was 4.6 months. The ORRITT was 73.7% (14/19) and no complete response was achieved. The ORRcombination was 66.7% (10/15). The DCRITT and DCRcombination were all 100% . (Not included 1 died). The median OS was not reached. Conclusions: This study proves that pembro alone and combined with standard chemotherapy has good efficacy and safety in locally recurrent HNSCC, and the statuses of TP53 and PI3K may be an important factor for the prognosis of immunotherapy. Acknowledgement: Thanks MSD China Medical Affair oncology team for giving scientific support. Clinical trial information: ChiCTR2100046731 . [Table: see text]