bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avelumab plus axitinib for first-line treatment of advanced renal cell carcinoma: A real-world ambispective RAVE-Renal study.
Authors: Chubenko Viacheslav , Baklanova Olga , Kalpinskiy Alexey , Safina Sufiia , Lebedinets Andrey , Shkurat Alexey , Parsadanova Elvira , Turganova Maria , Petkau Vladislav , Tovbik Natalya , Tkacheva Elena , Anzhiganova Yulia , Novikova Olga , Bragina Varvara , Zukov Ruslan , Tsimafeyeu Ilya 
Published: August 2024

117 Background: In a phase 3 JAVELIN Renal 101randomized study, the combination of avelumab and axitinib demonstrated a significant improvement in progression-free survival (PFS; median 13.9 months) and objective response rate (ORR; 59.3%) among patients with metastatic clear-cell renal cell carcinoma (mRCC), leading to FDA approval as a first-line therapy. In our ambispective observational RAVE-Renal study, real-world data were gathered to assess the practical application and outcomes associated with the use of avelumab and axitinib in clinical settings. Methods: Patients were recruited from 13 sites, with data collected anonymously online. Key inclusion criteria were untreated mRCC and a minimum age of 18 years. Safety and efficacy assessments were conducted in all patients who received at least one dose of avelumab and axitinib. The primary endpoints included ORR and PFS, while secondary endpoints encompassed overall survival (OS) and the incidence of treatment-related adverse events (TRAEs). Results: At the time of data cutoff (February 03, 2024), a total of 125 patients were enrolled and treated. Median age was 61 years (range, 37-74). Patients were predominantly men (74.3%), previously nephrectomised (81.4%), had 2 and more metastatic sites (77.1%) including bone (24.3%), liver (15.7%), and brain (3%) metastases. IMDC risk was evaluated in 102 patients. Among these patients, 36 (35.3%) were categorized as having favorable risk, 50 (49%) as intermediate risk, and 16 (15.7%) as poor risk. The median number of avelumab infusions was 7 (range, 1-29). Table summarizes efficacy and safety data. Conclusions: The real-world study of first-line avelumab and axitinib therapy reveals comparable ORR and PFS to those observed in the pivotal clinical trial among patients with mRCC. The combination was well tolerated. Further follow-up of patients in the study is ongoing. Clinical trial information: KCRB01012022 . [Table: see text]
Utility of PET-CT for assessment of response to neo-adjuvant chemotherapy in breast cancer.
Authors: Valiyaveettil Deepthi , Malik Monica 
Published: August 2024

12 Background: Response to neo-adjuvant chemotherapy (NACT) is associated with prognosis in non-metastatic breast cancer and can potentially inform further therapeutic options. The aim of this study was to correlate post NACT response on PET CT with pathological response. Methods: All patients who underwent pre- NACT (baseline) and post NACT PET CT imaging with F-18 FDG in a dose of 5-7 MBq/kg body weight with a minimum of 185 MBq given intravenously were retrospectively analyzed. Scan was performed on GE Discovery 710 whole-body PET scan with 128 slice CT. Relevant clinical and imaging related details were extracted from the treatment records. Post NACT PET response (PERCIST criteria) in the primary tumor and nodes was correlated with the pathological response on the post surgical specimen. Analysis was done using Microsoft Excel and SPSS v20 (IBM SPSS). Results: The median age was 49 years (range 30-76 years). 83.1% of patients had node positive disease on baseline PET imaging (not pathologically confirmed). Post chemotherapy PET showed complete metabolic response in the primary tumor and regional nodes in 56.3% and 74% of patients respectively. Two patients had progressive local disease. Pathological complete response rates post surgery in triple negative, Her2 neu positive and ER positive group was 50%, 34% and 12% respectively. The sensitivity, specificity, positive predictive value and negative predictive value is tabulated below. Conclusions: Overall FDG PET CT showed good specificity with limited sensitivity for post NACT response assessment in breast cancer. Our results suggest that post NACT PET CT may have limited utility for clinical decision making and at present its use cannot be recommended outside of a clinical trial.[Table: see text]
Analysis of prognostic factors in uterine cervical malignancy treated with concurrent chemoradiation therapy: A retrospective study in two centers in Korea.
Authors: Lee Seung-Mi , Lee Juhun , Lee Hyun Jung , Song Seungho , Heo Yujin , Lee Jieon , Kim Hee Jung 
Published: August 2024

125 Background: Cervical cancer is prevalent in most developing countries, and immune checkpoint inhibitors are very expensive to be standard treatment in limited-resource conditions. In these circumstances, concurrent chemoradiation therapy (CCRT) remains a preferred treatment. This study aims to evaluate prognosis and identify prognostic markers in cervical cancer patients treated with CCRT in Korea. Methods: This retrospective study utilized data from two centers (KNUH and KNUCH) January 2012 to September 2023. Disease stage was determined based on the FIGO 2018 system, including patients between stages IIB to IIIC-2. PET/CT assessed lymph node status. All patients received CCRT as the first-line treatment with cisplatin (40 to 60 mg/m2) chemotherapy and EBRT with or without ICR, guided by gynecologic radiation oncologist. Pelvic MRI or CT within 5 months after CCRT was used to evaluate radiosensitivity, including the size of the residual primary cervical tumor. The primary endpoint was 5-year disease-free survival (DFS), determined via systemic imaging studies like concurrent chest and abdomen CT or PET/CT. Median DFS was evaluated using Kaplan-Meier survival analysis. Prognostic factors were stratified and analyzed using Cox’s proportional hazard ratio regression. Multivariate analysis was conducted using only significant factors identified in the univariate analysis. Receiver operating characteristic curve and Youden’s index were used to determine the cutoff value. Results: Ninety-seven patients were enrolled. The median DFS within 5 years was not reached; mean DFS was 41.5 months (95% CI=36.2–46.8). Multivariate Cox’s proportional hazard regression identified two significant clinical factors for 5-year DFS; residual primary tumor size after CCRT and initial serum CA-125 level (p=0.001, p=0.007, respectively). The cutoff values were 1.85 cm for residual primary tumor size and 24.650 U/mL for CA-125 to predict the 5-year DFS rate (CR or NED vs. PR, SD, PD or recurrence). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for residual tumor size (36.4%, 98.4%, 92.3%, 73.4%, respectively) and CA-125 (67.9%, 60.7%, 46.3%, and 79.1%, respectively). Conclusions: The size of the residual primary tumor or initial serum CA-125 level can be useful in predicting 5-year DFS rate after CCRT. [Table: see text]
Exploration of the application of the sprayed γ-GGT fluorescent probe for visual imaging of epithelial ovarian cancer.
Authors: Zhang Manlin , Liu Zhihui , Qiu Lin , Ma Wenxin , Yang Zhuo 
Published: August 2024

127 Background: To explore the feasibility, accuracy and related influencing factors of spraying γ -GGT fluorescent probe in visual imaging of epithelial ovarian cancer. Methods: This study employed a previously developed spray-type γ-GGT fluorescent probe in fresh ex vivo epithelial ovarian cancer tissues. The experimental group selected ovarian cancer lesions of varying sizes and observed fluorescence imaging after spraying different concentrations of the probe. The optimal imaging concentration and observation time were determined based on pathological results. The validation group then used the optimal parameters to image primary and metastatic lesions, normal tissue, and suspicious areas, confirming the probe's accuracy. Clinical data from patients, such as age and stage, were analyzed to identify factors affecting probe imaging. Results: A total of 16 cases of epithelial ovarian cancer were included in this study, 8 cases were in the experimental group and 8 cases were in the validation group, and the samples were collected from the primary ovarian lesions, omental metastases and peritoneal metastases. In the experimental group, 42 lesions of 3 different diameters were collected. The visible lesions were not found to have any changes in the imaging within 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value within 1min-1h was between 1.26-1.29, with no statistical difference ( P>0.05), and the visible effect of 5 h was weaker or even invisible to the naked eye, and the best observation time was 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value of 1min-1h after spraying 10 μM of γ-GGT fluorescent probe was significantly higher than that of 1 μM and 5 μM ( P<0.05), and the best visible effect was achieved by the naked eye, resulting in a minimum effective imaging concentration of 10 μM. A total of 27 points were collected from the lesion with a diameter of <0.3 cm and its surrounding normal tissues with a distance of 1 cm or tissues with a diameter of 1-1.5 cm with a height of suspicion but normal to the naked eye, and 26 of the 27 tissues were confirmed by pathology to be cancerous and 1 was non-cancerous, with a true positive rate of 96.3% and a false positive rate of 3.7%. The overall true positive rate of fluorescence imaging was 98.6%. Univariate analysis showed that there were significant differences in the level of preoperative γ-GGT and the SBR value of preoperative treatment (all P<0.05), and the results of multivariate analysis showed that preoperative treatment was an independent influencing factor for fluorescence imaging of γ-GGT fluorescent probe ( P<0.05). Conclusions: This study tested the γ-GGT fluorescent probe for ovarian cancer imaging, finding 10 μM as the effective concentration and 1 minute to 1 hour as the optimal observation window. The probe's effectiveness is influenced by preoperative treatments.
The prognostic value of deep learning-based percentage of tumour-infiltrating lymphocytes in nasopharyngeal carcinoma.
Authors: Lu Tianzhu , Xie Fei , Zhan Shenghua , Hu Yujun , Zhong Fangyan , Chen Junjun , Pan Jian-ji , Xiong Xiaopeng , Lin Shaojun , Gong Xiaochang , Lin Shaojun , Guo Qiaojuan , Chua Melvin L.K. , Li Jingao 
Published: August 2024

133 Background: To calculate the percentage of tumor-infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) using deep-learning (DL) algorithms based on digital pathology images and differentiate the outcome. Methods: We recruited 435 patients with primary non-metastatic NPC and 63 patients with de novo metastatic NPC received immunotherapy. TILDL percentage was calculated using the convolutional neural network model, and its ability to differentiate metastasis risk and independent prognostic value were analyzed using Kaplan–Meier survival and multivariate analyses (MVA). Results: The median follow-up time of the training and validation cohorts was 69, and 76 months, respectively. Kaplan–Meier survival analysis showed that the 5-year distant metastasis-free survival (DMFS) and overall survival (OS) of patients with high TILDL were significantly better than those of patients with low infiltration. MVA showed that TILDL degree is an independent prognostic factor for DMFS (training cohort: HR=0.197, 95% CI: 0.077-0.503, p=0.001; validation cohort: HR=0.119, 95% CI: 0.028-0.503, p=0.004) and OS (training cohort: HR=0.418, 95% CI: 0.200-0.873, p=0.020; validation cohort: HR=0.158, 95% CI: 0.048-0.520, p=0.002). The concordance index (C-index) of TILDL was higher than that of the immunohistochemical CD3+, CD8+ T-cell, and CD20+ B-cell densities in terms of the DMFS and OS prediction accuracy. In an immunotherapy cohort of de novo metastatic NPC (n=63), MAV revealed that high TILDL percentage were an independent prognostic factor for PFS (HR=0.368, p= 0.008). Conclusions: TILDL percentage exhibited discriminative capabilities regarding the risk of metastasis and mortality in non-metastatic NPC, and has potential to be a biomarker for dmNPC received immunotherapy. This model will help select patients with a high risk of metastasis and provides a reference for improved individualized treatment.
Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.
Authors: Peng Xingchen , He Xuan , Zhang Weiwei , Huang Hai , Li Xue , Chen Jie , Wei Yuquan , Song Xiangrong 
Published: August 2024

139 Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]
HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.
Authors: Ghosh Adrija , Dagar Abhilash , Izzuddeen Yousra , Vivekanandan Abiramasundari , Raj Jaswin , Hazarika Sangeeta , Nair Ambily , Panda Smriti , Sharma Jyoti , Singhal Abhinav , Das Kalpa , Bhasker Suman , Thakar Alok , Mallick Supriya , Sharma Daya Nand , Sharma Aman 
Published: August 2024

143 Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage & HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute & late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A & 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p<0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p<0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT & OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .
Hypomagnesemia as a predictor of the efficacy of combination EGFR-targeted drugs versus EGFR ADCs alone in HNSCC.
Authors: Jiang Siqing , Liu Hanchun 
Published: August 2024

146 Background: EGFR-targeted drugs and ADCs in combination with EGFR-conjugated chemotherapy drugs can both cause hypomagnesemia. However, the predictive value of hypomagnesemia in response to treatment for head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: This study retrospectively analyzed patients who participated in clinical trials of EGFR-targeted drugs and EGFR ADCs for HNSCC and solid tumors, from February 24, 2022, to March 25, 2024. The primary endpoint of the study was time to treatment failure (TTF). Results: This study conducted a retrospective analysis of 68 patients . All patients exhibited normal baseline serum magnesium levels prior to treatment, but following two cycles of treatment, varying degrees of hypomagnesemia were observed among them. Among the 46 patients who received 2 cycles of combination therapy with EGFR-targeted drugs, 33 were hypomagnesemia and 13 were normal serum magnesium, ORR[90.9%vs. 8.5%,(P=0.002)] (Table), TTF [151 days (95% CI: 212-380) vs. 87 days (95% CI: 52-230), HR 0.576 (95% CI: 0.270–1.230,P = 0.021)]. Among the 22 patients who received EGFR ADC alone for 2 cycles, 8 were hypomagnesemia and 14 were normal serum magnesium, ORR [37.5% vs.28.6%, (P=0.549)] (Table), TTF [97.5 days (95% CI: 68-300) vs. 108.5 days (95% CI: 60-160), HR of 0.877 (95% CI: 0.339–2.263; P = 0.547)]. Conclusions: The study demonstrates that, the occurrence of hypomagnesemia is associated with ORR and TTF following two cycles of combination of EFGR-targeted drugs, not observed in patients receiving EGFR ADCs as monotherapy in HNSCC. [Table: see text]
Impact of acute therapeutic toxicities on anxiety during radiotherapy among Chinese patients with newly diagnosed nonmetastatic head and neck cancer: A cross-sectional study.
Authors: Li Fengyan , Zhou Guan-Qun 
Published: August 2024

147 Background: Head and neck cancer (HNC) poses a significant threat to both psychological and physical health. This study aimed to depict the anxiety status of Chinese newly diagnosed nonmetastatic HNC patients during radiotherapy (RT) and to examine predictors of anxiety symptoms. Methods: Newly diagnosed nonmetastatic HNC patients who received RT at the Radiation Therapy Center of Sun Yat-sen University Cancer Center from August 23,2023 to August 24,2023 were recruited into this study. Using Zung Self-Rating Anxiety Scale (Zung SAS) to screen anxiety. Twenty-four common acute therapeutic toxicities (18 patient-reported and 6 clinician-rated) were assessed according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-HN35) and Common Terminology Criteria for Adverse Events, fifth version (CTCAE V5.0). Chi-square ( χ2) test and multivariate binary logistic regression stepwise forward selection: likelihood ratio (LR) method were applied to identify factors associated with anxiety. Results: A total of 457 patients were included ultimately. Up to 29.10% of the patients showed varying degrees of anxiety and the average SAS standardized score was 45.66 ± 8.83. Chi-square test manifested that sex, annual household income, fatigue, anorexia, nausea, vomit, pain, dysphagia, sense problems (smell and taste), speech problems, trouble in social eating, trouble in social contact, sexual frustration, teeth problems, difficulty in opening mouth, xerostomia, sticky saliva, coughing, feeling ill, use of analgesics, use of nutritional supplements and weight loss were related to anxiety ( p < 0.05). But multivariate logistic regression only demonstrated fatigue (OR = 3.696, 95% CI = 2.096-6.519), speech problems (OR = 3.247, 95% CI = 1.554-6.783), sexual frustration (OR = 2.029, 95% CI = 1.232-3.341), nausea (OR = 3.075, 95% CI = 1.807-5.234), feeling ill (OR = 2.283, 95% CI = 1.215-4.291), use of nutritional supplements (OR = 1.930, 95% CI = 1.136-3.280) and difficulty in opening mouth (OR = 3.007, 95% CI = 1.081-8.363) as independent predictive factors of anxiety. Conclusions: The Chinese newly diagnosed nonmetastatic HNC patients suffered greatly from anxiety during RT. This study identified the predictive contribution of sociodemographic and clinical characteristics and 24 common acute therapeutic toxicities to the vulnerability to anxiety, which can provide evidence and reference for medical staff to carry out psychological intervention.