bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and biomarker analysis of neoadjuvant disitamab vedotin combined with immunotherapy in patients with muscle-invasive bladder cancer: A multi-center real-world study.
Authors: Hu Jiao , Yan Luzhe , Liu Jinhui , Chen Jinbo , OU ZHENYU , Chen Minfeng , Zu Xiongbing 
Published: August 2024

113 Background: Over half of the patients with muscle-invasive bladder cancer (MIBC) do not benefit from neoadjuvant chemotherapy due to cisplatin intolerance or resistance and have a poor prognosis. Antibody-drug conjugates (ADCs) have shown excellent clinical benefits in advanced MIBC in recent years, but there is a lack of studies using ADCs as neoadjuvant treatment. Methods: Patients with MIBC were eligible for inclusion criteria were included and received neoadjuvant RC48-ADC (disitamab vedotin) combined with toripalimab (n=79) or tislelizumab (n=23). The primary outcome was pathological downstaging, including complete pathological response (CR: pT0N0M0) and partial response (PR: pTa, Tis, and T1N0M0). The secondary outcome was disease free survival (DFS). Logistic regression and biomarker analyses were performed to identify efficacy predictors. Results: 102 patients from four hospitals were enrolled and evaluated for pathological staging. 84 patients (82.4%) had T2N0M0 tumors and 93 patients (91.2%) had pure urothelial carcinoma. 38 patients (37.3%, 95% CI: 27.9% - 47.4%) achieved CR and 77 patients (75.5%, 95% CI: 6.0% - 83.5%) achieved PR. The 1-year DFS rate was 97.4% (95% CI: 92.6% - 100.0%). Subgroup analysis showed that the clinical stage (P=0.001) and histological type (P=0.006) were independent efficacy predictors. However, there was no statistically significant difference between efficacy and HER2 status (P=1.000). Biomarker analysis showed that the enrichment of pathways, such as the extracellular matrix, angiogenesis, and lymphocyte chemotaxis, may be associated with better efficacy. Conclusions: Neoadjuvant RC48-ADC combined with immune checkpoint inhibitors showed promising efficacy in patients with MIBC, irrespective of HER2 expression. This study will expand neoadjuvant treatment strategies for patients who are intolerant to neoadjuvant chemotherapy. [Table: see text]
Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort study.
Authors: Yan Luzhe , Liu Jinhui , Chen Jinbo , Ou Zhenyu , Chen Minfeng , Zu Xiongbing , Hu Jiao 
Published: August 2024

115 Background: Neoadjuvant immunotherapy-driven bladder preservation (Neoimmu-CMT), despite its prominence, is constrained in application due to the absence of robust clinical evidence. Currently, there is a lack of comparative studies on the efficacy of Neoimmu-CMT versus the traditional trimodal therapy (TMT) or neoadjuvant chemotherapy- driven bladder preservation (NAC-CMT). To address this gap, our study (ChiCTR2300069303) aims to assess Neoimmu-CMT's viability and identify suitable candidates through a multicenter, propensity score-matched analysis. Methods: The study included 163 patients from 14 hospitals, categorized into Neoimmu-CMT (n=97), TMT (n=30), and NAC-CMT (n=36) subgroups. PSM was utilized to mitigate baseline variability. Primary outcomes were disease-free survival (DFS), bladder-intact DFS (BI-DFS), and overall survival (OS). Univariate and multivariate Cox analyses were used to identify potential prognostic factors. Biomarker assessment comprised immunohistochemistry and single-cell RNA sequencing. Results: Post-PSM, Neoimmu-CMT significantly outperformed NAC-CMT in DFS (HR: 2.112, 95% CI: 1.247-3.576, P=0.005) and BI-DFS (HR: 2.329, 95% CI: 1.138-4.770, P=0.021), with a 2-year BI-DFS rate of 90.28% compared to NAC-CMT's 71.59%. However, Neoimmu-CMT and TMT showed no significant difference in DFS and BI-DFS, with Neoimmu-CMT marginally surpassing TMT in 2-year BI-DFS rates (86.42% vs. 80.89%). Clinical complete response to neoadjuvant treatment and lower clinical T stage were positive prognostic factors for Neoimmu-CMT. Biomarker analysis showed the tumor microenvironment immune phenotype closely relates to bladder preservation outcomes. Conclusions: Neoimmu-CMT is a promising bladder preservation strategy, comparable to TMT and superior to NAC-CMT. Its advancement could significantly broaden bladder preservation treatment options. [Table: see text]
Prognostic value and therapeutic response of neutrophil-to-lymphocyte ratio in penile cancer.
Authors: Tan Xingliang , Yu Yiqi , Li Hang , Wu Weicheng , Chen Juexiao , Wu Zhiming , Yao Kai 
Published: August 2024

116 Background: Chronic inflammation mediated by poor genital hygiene is a well-recognized pathogenic trigger for penile squamous cell carcinoma (PSCC). The neutrophil-to-lymphocyte ratio (NLR) is a simple and reproducible factor reflecting the systemic inflammatory response and has been reported as an unfavorable indicator in PSCC. However, previous studies limited by small sample sizes, confounding prognostic features and without high-quality evidence to demonstrate the clinical significance of the NLR. Methods: A large cohort of 582 penile cancer patients who underwent radical inguinal lymphadenectomy with definitive pN stages were enrolled in this study. Univariate and multivariate Cox regression analyses were performed to investigate prognostic factors and inflammation-related markers in PSCC patients. More importantly, the propensity score matching (PSM) method was used to minimize the prognostic confounding clinicopathological features. Immunofluorescence was further used to investigate the correlation between tumor-infiltrating neutrophils, CD8+ T cells and the NLR. Results: According to the ROC curve, the optimal cutoff value for the NLR was 3.0, and 226 (38.8%) PSCC patients had a high NLR. Survival analyses indicated that advanced pT, pN, pathological grade, lymphovascular invasion, high NLR, C-reactive protein (≥ 2.2 mg/L) and serum amyloid A (≥ 11.3 mg/L) were associated with poor PFS and CSS. After PSM to eliminate interference from clinical factors, pN and the NLR were found to be independent prognostic indicators in PSCC patients (both p<0.001). Cox multivariate regression analysis revealed that the HR for PFS was 1.64 (1.15–2.34) in the high NLR group and 1.56 (1.04–2.34) in the high NLR group (p=0.006 and 0.030, respectively). PSCC patients with high NLRs experienced shorter PFS after receiving cisplatin-based chemotherapy (p=0.037) and PD-1 immunotherapy (p=0.020). In addition, we found that the infiltration of tumor-associated neutrophils (CD66+) and the CD8+ T-cell ratio were positively correlated with the NLR. The development and formation of neutrophil extracellular traps (NETs) might contribute to chemoresistance and tumor progression in high-NLR PSCC patients. Conclusions: In this study, we demonstrated that the NLR is an effective, simple and independent prognostic indicator for PSCC. The NLR holds promise as a powerful tool to guide decision-making in clinical practice. [Table: see text]
PSA response and cabazitaxel outcomes stratified by prior docetaxel PSA response in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Wee Christopher Eing , Nizam Amanda , Ornstein Moshe Chaim , Gilligan Timothy D. , Chen Xiaoying , Maroli Kimberly , Martin Allison , Bonham Amanda , Pietro Carolyn , Gupta Shilpa 
Published: August 2024

119 Background: In the TheraP trial, both cabazitaxel and lutetium Lu 177 vipivotide textraxetan demonstrated similar overall survival (OS) in patients with mCRPC previously treated with docetaxel. We seek to identify predictors for cabazitaxel benefit by evaluating patients’ cabazitaxel outcomes in the context of prior docetaxel outcomes. Methods: We identified patients who started cabazitaxel after January 2010 at our institution. Patients were included if they received docetaxel for mCRPC but excluded if they received docetaxel for hormone-sensitive disease, used taxane in combination with other agents (e.g. carboplatin), or received multiple courses of same taxane (e.g. “re-challenges”). For adequate assessment of PSA response, patients were only included if pre-chemo PSA was > 20 ng/mL and had received at least two cycles of both taxanes. PSA response was defined as >50% decrease from baseline sustained for at least 3 weeks (PSA50). OS was calculated from time of cabazitaxel start to death from any cause. Results: Eighty patients were identified with a median age of 70 years at cabazitaxel start. Forty (50%) patients had a PSA50 with docetaxel, while only 18.8% had a PSA50 with subsequent cabazitaxel. Patients who had a PSA50 to docetaxel had a significantly higher chance of PSA50 to cabazitaxel (OR 5.29, 95% CI: 1.36, 20.53, p = 0.0162); the PSA50 rates on cabazitaxel were 30% and 7.5% between those that did and did not have a PSA50 to docetaxel, respectively. There were no significant differences in cabazitaxel median OS based on prior docetaxel PSA50. Conclusions: Patients who had PSA50 to docetaxel had a significantly higher chance to have a PSA50 to cabazitaxel. Prior docetaxel PSA50 could be considered when deciding whether to use cabazitaxel or an alternative agent for subsequent treatment. [Table: see text]
Validation of FIGO 2018 staging for cervical cancer: Insights from a Japanese multicenter cohort.
Authors: Hamada Kohei , Yamanoi Koji , Taki Mana , Murakami Ryusuke , Yamaguchi Ken , Hamanishi Junzo , Mandai Masaki 
Published: August 2024

126 Background: The International Federation of Gynecology and Obstetrics (FIGO) updated its staging system for cervical cancer in 2018, introducing major changes such as the establishment of stage IIIC based on lymph node metastasis (LNM), which has been reported to provide a better reflection of prognosis. However, stage IIIC has been reported to be heterogeneous, with prognoses varying depending on LNM extent and local tumor factors. In Japan, where various imaging tests are extensively performed, this revision is expected to lead to numerous cases of stage migration due to LNM. However, there have been few reports on the impact of this revision in Japan. Therefore, this multicenter study aims to assess the validity of FIGO 2018 in a Japanese cohort, focusing on LNM, local tumor factors, and histological types. Methods: Using a unified registry for gynecological malignancies developed by The Japanese Society of Obstetrics and Gynecology, this study involved 1,468 cervical cancer patients treated between 2011 and 2019 across eight designated cancer treatment hospitals. The registry used the FIGO 2009 staging system, and patients with stage IA to IIIB disease were restaged according to the FIGO 2018. Stage IIIC cases were further classified into substages IIIC-T1, IIIC-T2, and IIIC-T3AB based on local tumor factors. Results: After restaging process, A total of 347 cases (27.6%) were upstaged to stage IIIC according to LNM. Survival analysis showed that stage IIIC had a poorer prognosis than stage II (HR, 2.09; 95% CI, 1.27-3.44; p=0.004), but a significantly better prognosis than stage IIIAB (HR, 0.46; 95% CI, 0.27-0.77; p=0.004). There was also a clear difference between subclasses stage IIIC1 and IIIC2, with IIIC2 having a worse prognosis (HR, 2.13; 95% CI, 1.23-3.67; p=0.007). A survival analysis focusing on stageIIIC1 subdivisions (T1, T2, and T3AB) showed varied prognosis among them. Furthermore, IIIC1-T1 and IIIC1-T2 had significantly worse prognoses compared to stages I and II (I vs IIIC1-T1, HR, 3.21; 95% CI, 1.64-6.30; p<0.001. II vs IIIC1-T2, HR, 1.82; 95% CI, 1.03-3.21; p=0.04), while the prognosis of IIIC1-T3AB was similar to stage IIIAB. In the analysis by histological type, there was little difference between IIIC1-T1 and IIIC1-T2 in squamous cell carcinoma, but there was significant difference between IIIC1-T1 and IIIC1-T2 in adenocarcinoma (HR, 5.12; 95% CI, 1.10-23.74; p=0.04). On the other hand, for IIIC2, prognosis was similar across T1, T2, and T3AB, all showing uniformly poor outcomes. Conclusions: We were able to concretely clarify the current situation in Japan and validate the usefulness of FIGO 2018. The comprehensive examination of LNM, local tumor factors, and histological type may further reinforce and complement FIGO 2018.
Neoadjuvant treatment with trastuzumab and pertuzumab plus fulvestrant in older patients with HER2-positive, ER-positive early breast cancer.
Authors: Celis Juan Jose , Rodriguez Vanessa , Rodriguez Crismar 
Published: August 2024

13 Background: The prevalence of breast cancer in older adults (≥70 years) is increasing and worse outcomes compared to younger patients could be explained by advanced presentation, late diagnosis, deterioration of organ function, and the presence of multimorbidities. Older patients are under-represented in clinical trials. Therefore, the risks and benefits of anticancer therapy should be carefully evaluated. The CREATE-X36 and KATHERINE37 trials enrolled few older individuals but did not show any new safety concerns, older patients should be considered for trastuzumab in case of residual HER2-positive disease following neoadjuvant systemic therapy; neoadjuvant endocrine therapy for at least 4-6 months is useful for older patients who are not immediately suitable for surgery and aromatase inhibitors are favored over tamoxifen in view of better response rate. Although adjuvant trastuzumab is beneficial regardless of age, anti-HER2 (neo)adjuvant strategies remain poorly investigated in patients age 65 years or older. Pertuzumab can be considered for high-risk individuals, but diarrhoea can be debilitating in older adults, similarly with adjuvant neratinib. Age is associated with increased cardiac toxicity rates with trastuzumab,80 with 15–40% of patients requiring early discontinuation, particularly patients who are age 80 years or older and have multimorbidities. Methods: Open-label, exploratory, phase 2 study done at one center in Venezuela. Patients were eligible if they had previously untreated, histologically confirmed, unilateral, invasive, cN0, HER2-positive, ER-positive breast cancer and older >70y. Patients were treated every 3 weeks with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and intravenous pertuzumab (840 mg loading dose in the first cycle and then at 420 mg) and intramuscular fulvestrant (500 mg) every 4 weeks for four cycles. The coprimary endpoints were change from baseline in Ki67 expression at surgery and pathological complete response. Results: Between January, 2020, and June, 2023, we enrolled 12 patients. At baseline, geometric mean Ki67 expression was 42·9 and 12·1 at time of surgery (n=8; p=0·013). A clinical objective response immediately before surgery was achieved by 10 of 12 patients. At surgery, eight patients had a pathological complete response in breast and axillary nodes. The most frequent grade 3 adverse events was diarrhea (n=4), and stomatitis. No grade 4 or serious adverse events were recorded in the study and there were no deaths. Conclusions: The combination of fulvestrant, trastuzumab, and pertuzumab had a effect on the expression of Ki67 and pCR at surgery. Triple targeting of ER, HER2, could be an effective chemotherapy-free treatment strategy for older patiens. Further clinical testing and additional molecular characterisation is necessary.
Induction chemoimmunotherapy followed by radiotherapy in locally advanced head and neck squamous cell carcinoma: A real-world study.
Authors: Yang Yi , Wang Shun-Xin , Lei Yi-Ming , Mao Yan-Ping 
Published: August 2024

131 Background: Patients with locally advanced head and neck squamous cell cancers (LAHNSCC) present poor prognosis despite multi-disciplinary comprehensive treatment, and novel treatment strategies are urgently needed. Recently, several phase II clinical trials reported encouraging pathological complete response rate of induction chemoimmunotherapy (IC+ICI) in LAHNSCC, suggesting potentially long-term survival benefits. Therefore, we conducted this real-world study to compare the efficacy of IC+ICI followed by radiotherapy (RT) versus induction chemotherapy (IC) followed by RT in LAHNSCC. Methods: We retrospectively included patients with LAHNSCC from Sun Yat-sen University Cancer center database treated with IC+ICI followed by RT or IC followed by RT between 1/2018-12/2021. Survival outcomes and adverse effects (AEs) were compared between the two groups. Results: A total of 262 patients were included: 128 (48.9%) in the IC+ICI group, and 134 (51.1%) in the IC group. Median age for the whole cohort was 60 (53–66) years, and the male-to-female ratio is 8.9:1. Most patients (84.4%) had stage IV disease. The median follow-up time was 26.7 (IQR 25.8-29.6) months. Marginally significant higher objective response rate (ORR) was observed in the IC+ICI group than that in the IC group (81.25% vs 72.39%, P=0.09). Patients in the IC+ICI group had significantly better results than those in the IC group in 2-year overall survival (OS; 88.9% vs. 71.5%, P<0.001), disease-free survival (DFS; 77.5% vs. 58.3%, P=0.005), locoregional relapse-free survival (LRRFS; 78.4% vs. 59.7%, P=0.009) and distant metastasis-free survival (DMFS; 87.5% vs. 64.6%, P<0.001). Multivariate analysis confirmed that combining immunotherapy in the induction stage was an independent prognostic factor for OS (HR 0.40, 95%CI 0.19-0.84), DFS (HR 0.45, 95%CI 0.28-0.72), LRRFS (HR 0.56, 95%CI 0.31-0.99), and DMFS (HR 0.37, 95%CI 0.19-0.73). The incidences of G3/4 AEs between the IC+ICI group and the IC group were comparable during the induction stage (6.25% vs 12.69%, P = 0.076) as well as the radiotherapy stage (14.06% vs 14.18%, P = 0.978). Conclusions: This study firstly reported that IC+ICI followed by RT was superior to IC followed by RT in long-term survival outcome in LAHNSCC.
Analysis of proliferating Treg cells as a predictor for immunotherapy response using systemic longitudinal immune profiling: Biomarker analysis of the phase 3 CONTINUUM trial.
Authors: Huang Saiwei , Jiang Wei , Zhang Yuan , Xu Sha , Wang Yaqin , Yang Kunyu , Zhang Ning , Liu Fang , Zou Guorong , Jin Feng , Wu Haijun , Zhou Yangying , Zhu Xiaodong , Chen Nianyong , Xu Cheng , Liu Na , Sun Ying , Ma Jun , Liang Ye-Lin , Liu Xu 
Published: August 2024

140 Background: The discovery of predictive biomarkers for immunotherapy is hindered by the lack of control groups in most translational studies, making it impossible to discern whether the identified biomarkers are merely prognostic or truly predictive for treatment outcomes. This study reported on prospectively designed biomarker analyses of the phase 3 CONTINNUUM trial (NCT03700476), the first trial that demonstrated prolonged event-free survival (EFS) with the addition of anti-PD-1 (aPD1) to chemoradiotherapy (CRT) in locoregionally-advanced nasopharyngeal carcinoma (LA-NPC). Methods: Mass cytometry was performed to generate a dynamic single-cell atlas on longitudinal peripheral blood mononuclear cell (PBMC) samples from 12 pairs of matched patients with or without relapse in the aPD1-CRT arm. The machine-learning algorithm CellCnn was applied to identify a cell subset that was most strongly associated with disease relapse, which was further confirmed by flow cytometry (n = 120). Single-cell RNA sequencing data from matched PBMC and tumor samples were analyzed and multiplex immunohistochemistry was performed on baseline tumor samples (n = 249) to verify the predictive value of the cell subset within tumors. Results: Baseline circulating regulatory T cells (Tregs), with a Ki67+ proliferating phenotype, were found to display a higher frequency in LA-NPC patients who developed posttreatment relapse ( P < 0.001), which was further validated by flow cytometry. The intratumoral Ki67+ Tregs were also identified and correlated with an immunosuppressive tumor microenvironment. In patients with a low baseline level of Ki67+ Tregs, additional aPD1 significantly improved EFS compared with CRT alone (log-rank P = 0.011, HR = 0.22, 95% CI: 0.06−0.79), while EFS was almost identical in both treatment arms in patients with high Ki67+ Treg levels (log-rank P = 0.995, HR = 1.00, 95% CI: 0.49−2.05; interaction P = 0.047). This predictive value was further validated in datasets from two independent randomized trials in renal cancer. Conclusions: The frequency of Ki67+ Tregs can serve as a reliable predictive tool in selecting patients who are more likely to benefit from immunotherapy, potentially informing individualized immunotherapy strategies.
Radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy in patients with low-risk nasopharyngeal carcinoma: Updated results from a multicenter, open-label, non-inferiority, randomized phase III trial.
Authors: Guo Rui , Zhang Yuan , Zhang Ning , Deng Bin , Cheng Zhi-Bin , Huang Jing , Zhang Fan , Mao Yan-Ping , Li Wen-Fei , Zhou Guan-Qun , Chen Yu-Pei , Xu Cheng , Lin Li , Zhang Wei-Wei , Jiang Xu , Liu Qing , Sun Ying , Ma Jun , Chen Lei 
Published: August 2024

142 Background: There is limited evidence for the role of concurrent chemotherapy with use of intensity-modulated radiation therapy (IMRT) in low-risk stage II/T3N0 Nasopharyngeal Carcinoma (NPC) patients. We previously reported comparable 3-year failure-free survival-free survival (FFS) using radiotherapy alone compared with concurrent chemoradiotherapy in the low-risk patients. Here, we present the 5-year overall survival (OS) analysis and additional analysis. Methods: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. This trial is registered with ClinicalTrials.gov, number NCT02633202. Results: In this randomized trial, patients were assigned to be treated IMRT alone (n=172) or with concurrent chemoradiotherapy (IMRT with cisplatin, n=169). With a median follow-up of 70.1 months, the IMRT-alone group had a similar 5-year overall survival (95.2% vs. 98.2%, hazard ratio, 2.27 [95%CI:0.70-7.40]; P=0.16), failure-free survival (86.2% vs. 88.4%, hazard ratio, 1.16 [95%CI:0.64-2.07]; p = 0.63). Hearing impairment (HI) data (assessed by The Hearing Handicap Inventory for Adult- Screening version (HHIA-S)) were collected from 86 patients in the IMRT-alone group and 81 patients in the concurrent chemoradiotherapy group. Among the patients, 45(26.9%) developed HI (IMRT-alone vs. CCRT: 20 [23.3%] vs. 25 [30.9%]), among which 36 (21.6%) had mind HI (IMRT-alone vs. CCRT: 15 [17.4%] vs. 21 [25.9%]). Conclusions: Radiotherapy alone provides comparable survival or disease control and less toxicity compared to CCRT in low-risk nasopharyngeal carcinoma. Clinical trial information: NCT02633202 .