bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of enhanced recovery after radiotherapy (ERAR) on the quality of life in patients with nasopharyngeal carcinoma after radiotherapy: A randomized controlled trial.
Authors: Lin Nan , Zhou Xueyan , Ma Xuelei 
Published: August 2024

12128 Background: Nasopharyngeal carcinoma (NPC) is a common disease in Southern China and Southeast Asia. Radiotherapy is an essential treatment for locoregionally advanced NPC (LA-NPC). Although Enhanced Recovery After Surgery (ERAS) is widely used in surgical settings, the guidelines do not systematically address the specific roles of various disciplines involved in radiotherapy rehabilitation. Therefore, we propose the concept of Enhanced Recovery After Radiotherapy (ERAR), which is considered to be a vital complement to radiology. Methods: We enrolled patients with stage III to IVA LA-NPC in this study. Participants completed baseline surveys before random assignment. ERAR interventions were implemented during radiotherapy to develop systematic management plans in the aspects of nursing, oral care, psychology, rehabilitation, nutrition, and skin health. The control group received conventional radiotherapy. Outcomes were evaluated at the 17th and 33rd radiotherapy sessions. We used generalized estimating equations to evaluate group by time effects on the outcomes, controlling for key covariates. Results: A total of 108 LA-NPC patients with a mean age of 48.3 ± 11.0 years were enrolled in the study group from August 2021 to September 2023. Across all time points, the ERAR group showed significant improvements in Hospital Anxiety and Depression Scale (HADS) anxiety ( P <.001), HADS depression ( P <.001), distress thermometer ( P =.049), quality of life ( P =.014), NRS2002 ( P =.040), weight loss ( P <.001), and Oral Health Impact Profile-14 (OHIP-14) ( P =.040) scores compared with the conventional care group. Conclusions: The ERAR pathway has a significant benefit on reducing acute radiation-induced toxicity in patients with LA-NPC. It is hoped that this study will provide a reference for clinicians and promote the implementation of a standardized protocol for rapid recovery from radiotherapy. Clinical trial information: ChiCTR2300075874. [Table: see text]
Racial disparities and survival outcome of patients with locally advanced cervix cancer in the international randomised phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274).
Authors: Lee Yeh Chen , Castellano Tara , Myers Tashanna K. N. , Barnes Elizabeth H , Chase Dana Meredith , McCormick Colleen , Diamante Katrina , Shannon Catherine M. , Huh Warner King , Lea Jayanthi Sivasothy , Walker Joan L. , Small William , Miller Katherine , Govindarajulu Geetha , Monk Bradley J. , Stockler Martin R , Moore Kathleen N. , Mileshkin Linda R. , Bae-Jump Victoria Lin 
Published: August 2024

1594 Background: OUTBACK was an international multi-center phase 3 trial investigating adjuvant chemotherapy following definitive chemoradiation in locally advanced cervix cancer. We analysed if baseline characteristics were associated with survival outcome. More specifically, we determined whether race held prognostic significance relative to established clinical factors. Methods: We compared baseline characteristics (encompassing demographics, biomarkers and participants’ self-ratings of EORTC QLQ-C30 scores) between racial groups using chi-squared tests. We then explored relationships between baseline characteristics and survival outcomes using univariable and multivariable Cox proportional hazards regression models with stepwise selection. Results: Black or African American participants accounted for 13% (n=121/919) of the OUTBACK study population. There were no evident differences in the proportion of Black or African American participants, as compared to other racial groups, across most baseline characteristics, except for country of residence (USA vs non-USA, p<0.01). When examining the impact of race (Black or African American vs other racial groups) on survival outcomes in locally advanced cervix cancer, we found no evident associations with overall survival (HR 1.2; 95%CI,0.84 – 1.72; p=0.32) or progression free survival (HR 1.29; 95%CI, 0.95 – 1.75; p=0.10). Multivariable analysis identified several independent prognostic factors for overall survival, including performance status (HR 1.43; 95%CI, 1.04-1.95; p=0.03), FIGO stage (HR 2.02; 95%CI, 1.48-2.75; p<0.01), nodal involvement (HR 1.59; 95%CI, 1.18-2.14; p<0.01), and elevated white cell count (HR 1.68; 95%CI, 1.21-2.33; p<0.01). Role function, social function, financial difficulties and eGFR showed significance in univariable analysis for overall survival but did not retain significance in multivariable analysis. These findings were consistent when examining progression-free survival. Conclusions: No discernible disparities in survival outcomes were observed between Black or African American participants and other racial groups undergoing primary treatment for locally advanced cervix cancer. The primary prognostic determinants for this disease continue to be cancer staging and clinical performance status. Enrolment into a clinical trial may have abrogated the historical disparities seen among ethnic and racial groups. Clinical trial information: 12610000732088.
Efficacy and safety of recombinant human adenovirus type 5 (H101) combined with immune checkpoint inhibitors (ICIs) in patients with liver metastatic gastric cancer: A prospective multicenter phase II study (the TROJAN 021 study).
Authors: Yuan Min , Xu Jing , Zhu Zhongzheng , Liu Zhuqing , Mao Wei , Wang Hui , Mao Dongliang , Zhan Qiong , Li Xiaoping , Zheng Leizhen , Liang Xiaohua , Wang Mei , Xu Qing 
Published: August 2024

2635 Background: Immune checkpoint inhibitors (ICIs) have shown significant efficacy in metastatic gastric cancer, but some patients may not respond to them because of immune resistance. Recombinant Human Adenovirus Type 5 (H101), the world’s first oncolytic virus antitumor drug in China, can induce cell death, expose tumor antigens, provide adjuvants for anti-tumor immune priming, and potentially increase responsiveness to immunotherapies. Here, we presented the efficacy and safety of H101 combined with immune checkpoint inhibitors (ICIs) in patients with liver metastatic gastric cancer. Methods: In this multi-center, phase II trial (the TROJAN 021 study, ChiCTR1900027922), patients with liver metastatic gastric cancer received 2 cycles of H101 ultrasound guided injections into liver lesions, bi-weekly in combination with anti-PD-1 antibodies and chemotherapy bi-weekly until progression or intolerable toxicity. The primary objective was safety and objective response rate (ORR). Secondary objective included progression-free survival (PFS), overall survival (OS) and disease control rate (DCR). Efficacy assessments were performed every 4 weeks following RECIST v1.1 criteria. PFS and OS were estimated using the Kaplan-Meier method. Results: From September 2020 to September 2022, 21 patients were enrolled. Of them, 18 were males, median age was 66 years (range: 36-71) and ECOG performance status was either 0 (n=15) or 1 (n=6). 10 patients (47.6%) received as first-line therapy, 1 (4.8%) as second-line and 5 (23.8%) as third line and above therapy. The primary endpoint was met with a median PFS of 4.8 months. The median OS was 13.2 months. Objective tumor responses were CR (n=0), PR (n=7), SD (n=12) and PD (n=2). ORR was 33.3% (7/21), and DCR was 90.5% (19/21). Treatment related adverse events (TRAE) occurred in 12 patients (57.1%). The most frequently observed TRAEs were injection site pain (48.1%), fever (57.1%) and fatigue (23.8%). Three patients (14.3%) had grade 3 treatment-related adverse events. There were no grade 4 and 5 treatment-related adverse events. Grades 3 toxicities included neutropenia (2/21, 9.5%) and hypertension (1/21, 4.8%). Conclusions: These promising results show that combination of Recombinant Human Adenovirus Type 5 (H101) and ICIs demonstrated acceptable toxicity and promising antitumor efficacy in patients with liver metastatic gastric cancer. Further validation of the efficacy in a randomized prospective trial is warranted. Clinical trial information: ChiCTR1900027922.
Neoadjuvant immuno-chemo-radiotherapy in operable esophageal and gastroesophageal junction adenocarcinoma with carboplatin, paclitaxel plus radiotherapy and avelumab (anti-PDL1 antibody): Neo-CREATE trial.
Authors: Roy Amitesh Chandra , Bright Tim F , Singhal Nimit , Burge Matthew E. , Segelov Eva , Haydon Andrew Mark , Chantrill Lorraine A. , Michael Michael , Connell Caroline , Moffat David , Woodman Richard John , Michael Michael , Symonds Erin , Price Timothy Jay , Scott-Hoy Alex , Richards Alison , Karapetis Christos Stelios 
Published: August 2024

4086 Background: Neoadjuvant CROSS regimen followed by adjuvant nivolumab or perioperative FLOT are current standards of care for patients with curable esophageal/ gastroesophageal (GEJ) junction adenocarcinoma. We hypothesized that adding avelumab to neoadjuvant chemo-radiation (CRT-A) before surgery can further improve outcomes. Methods: Patients with cT1-3 and N0/N1 M0 esophageal or GEJ adenocarcinomas eligible for curative surgery received weekly carboplatin and paclitaxel concurrently with radiotherapy (41.4 Gy in 23 fractions) and bi-weekly avelumab (5 doses). The trial had a run-in phase of 10 patients to evaluate feasibility and safety and a planned futility analysis after 15 patients have undergone surgery. The primary endpoint was pathological complete response (pCR) (Mandard criteria) by central pathology review, secondary endpoints were major histological response and survival outcomes. Using an A’hern single stage design for efficacy forty-seven patients were required to rule out a lower limit of a 20% pCR rate (p0) and to demonstrate an increase to a 40% pCR rate (p1), with 90% power and significance level α=0.05. Tissue, blood, and stool samples were collected for corelative analysis. Results: 48 patients were enrolled between Sept 2019 to Oct 2022 across seven Australian sites. Median age 65 [44-81], 95% were male (n=45), with majority of cancers being esophageal/GEJ type I (n = 35), with GEJ type II (n = 13). Forty-seven (97%) patients completed CRT -A and 46 (95%) had surgery. CRT-A was well tolerated, with two patients having > grade 2 adverse event of interest in the form of myocarditis attributed to avelumab. Notable toxicities included grade 2-4 myocarditis (4%), anastomotic leak (4%), infection (6%) and diarrhoea (6%). In 44 evaluable patients, pCR was 23%. MHR was 58.3% (95% CI, 43.3%-72.1%), complete or near complete response (Tumor Regression Grade 1-2) was 31%. Overall, 1-yr disease free survival was 83.8% and OS was 91.2%. 1-yr disease free survival was 91.7% for patients with MHR vs 73.3% without MHR, p=0.20. Conclusions: Combining avelumab with neoadjuvant CRT is feasible in patients with acceptable tolerability in locally advanced esophageal/ GEJ adenocarcinoma. Avelumab with CRT is active however observed pCR rate does not represent a signal of substantial improvement compared to historical controls. Exploratory analysis suggests improved outcomes in patients with optimal tumour regression after neoadjuvant CRT-A. Exploratory biomarker work to corelate with outcomes is underway. Clinical trial information: ACTRN12619000288123.
Phase II study of pirfenidone combined with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.
Authors: Guo Guifang , Li Shengping , Mao Yize , Yang Qiuxia , Yao Zehui , Wang Jun 
Published: August 2024

4152 Background: Pancreatic cancer is a disastrous malignancy characterized by the dense fibrous stroma, elevating interstitial pressure and impairing perfusion of chemotherapeutics. Pirfenidone (PFD) is an oral antifibrotic agent, which might reduce the degree of fibrosis of pancreatic cancer and increase drug delivery. Thus, we aimed to evaluate the efficacy and safety of pirfenidone (PFD) plus nab-paclitaxel and gemcitabine (AG) for patients with metastatic pancreatic cancer. Methods: In this two-stage single-arm phase II trial, treatment-naïve patients with metastatic pancreatic cancer received oral PFD, 200 mg three times daily in the first week and 400 mg three times daily thereafter, in combination with intravenously administered gemcitabine 1000 mg/m2 and nab-paclitaxel 120 mg/m2 on days 1,8 of each 21-day cycle. The primary endpoint was overall response rate (ORR). A total of 33 patients were required based on the assumption of an expected ORR of 45%, with an α-error of 5% (one-sided) and a β-error of 20%. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: We enrolled 33 patients from October 2020 to February 2023, with median age of 61years (IQR 53-65), 21(63.6%) male and 12(36.4%) female. Metastatic sites included the liver (32cases), lung(7cases) and peritoneum (11cases). The last one patient was enrolled on February 24, 2023 and the deadline of follow up was Jan 25, 2024, with only one was unevaluable. The ORR was 50.0% (95% CI 33.6%-66.4%) and the DCR was 93.8%(95%CI 79.9%-98.9%). The median PFS was 4.9 months (95% CI 3.9-5.9) and the median OS was 9.1 months (95% CI 7.8-10.4). Among all cases of 25 with elevated CA19-9 at diagnosis, 56% patients experienced a decrease in CA19-9 levels of more than 50%. Grade 3-4 toxicities were observed in 11 (34.4%) patients, with leukopenia (7[21.9%]), anemia (5[15.6%]) and elevated AST level (4[12.5%]). No treatment-related deaths occurred. Conclusions: Adding PFD to AG showed promising ORR and DCR and an acceptable adverse event in patients with metastatic pancreatic cancer. Clinical trial information: ChiCTR2000034397.
Tislelizumab combined with gemcitabine and albumin paclitaxel as preoperative therapy for patients with borderline resectable pancreatic cancer: A prospective, single-arm, phase II trial.
Authors: He Yonggang Gang , Huang Xiaobing , Zheng Lu , Li Jing , Zhao Chongyu , Li Ying , Zuo Guohua 
Published: August 2024

4162 Background: Pancreatic cancer is a highly aggressive disease with low resection rate and poor prognosis. Neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) is increasing in acceptability, but no standard treatment has been established. Herein, we aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with BRPC. Methods: This is a single arm, exploratory phase II clinical trial. Gemcitabine (1000 mg/m2) and albumin paclitaxel (125 mg/m2; AG) were administered to patients with BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Surgical intervention was assessed after two cycles of treatment. Primary endpoint was adverse events (AE) and R0 resection rate. Secondary endpoints were objective response rate (ORR) and progression free survival (PFS) by mRECIST, relapse-free survival (RFS) and overall survival (OS). Results: Between October 2022 and December 2023, 21 patients were enrolled in the study. At the end of the last follow-up (January 27, 2024), 15 patients had a best response of partial response, the ORR was 71.4% according to mRECIST. The disease control rate (DCR) was 85.7%. The 12-months PFS rate, and 12-months OS rate were 68.2% (95% CI: 38.0%–86.0%), and 63.8% (95% CI: 33.2%–88.3%), respectively. After the two cycles of neoadjuvant therapy, 14 patients underwent resection (66.7%,14/21) and the R0 resection rate was 100%. For those patients who did not undergo surgery, 3 of them achieved PR but refused surgery, 3 patients developed disease progression and lost the chance of surgery. 1 patient died of severe pneumonia caused by H1N1 infection. So far the safety of neoadjuvant treatment was satisfied, no grade 4 or above treatment-related-adverse events (TRAEs) were observed. Grade 3 TRAEs were reported in 3(14.29%) patients. Frequently occurring adverse events were grade 1-2, including myelosuppression (90.47%), albuminuria (80.95%), nausea (61.90%), elevated aspartate aminotransferase (47.62%) and elevated alanine aminotransferase (38.10%). Grade 3 or higher adverse events were pneumonia (4.76%), elevated AST (4.76%), elevated ALT (4.76%) and myelosuppression (4.76%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy displayed promising antitumor activity and acceptable safety profile for patients with BRPC. Clinical trial information: ChiCTR2200063680.
Efficacy of cytotoxic chemotherapy in recurrent/metastatic adenoid cystic carcinoma (ACC).
Authors: Wotman Michael , Hoff Camilla Oliveira , Bonini Flavia , Sawyer Matthew , Wang Kaiwen , Andreazza Dal Lago Eduardo , Guimaraes de Sousa Luana , Ferrarotto Renata 
Published: August 2024

6111 Background: Despite aggressive local therapy, many ACC patients (~50%) develop recurrent and/or metastatic (R/M) disease. However, there is no standard of care or FDA-approved systemic therapy for this population. Based on small phase II trials, mostly including multiple salivary gland histologies, cytotoxic chemotherapy is recommended for symptomatic patients with high tumor burden, but its efficacy and impact on survival in R/M ACC remain unsubstantiated. Methods: A retrospective cohort study was conducted at MD Anderson Cancer Center with an institutional ACC database (N=769). Patients diagnosed with R/M ACC and treated with single-agent or combination palliative-intent chemotherapy were included. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST 1.1. Secondary endpoints were median overall survival (mOS) and progression-free survival (mPFS) on chemotherapy for the entire cohort and stratified by growth pattern (solid v non-solid), line of therapy (1 v >2), chemotherapy regimen, and stage at diagnosis (M0 v M1). Results: 48 out of 115 patients who received chemotherapy were evaluated for response per RECIST.Median age at diagnosis was 43.6 years. 56% were male, 79% had M0 stage at diagnosis, 67% had minor salivary gland primary tumors, 52% had solid growth pattern, 31% had non-solid growth pattern, and 54% received first-line chemotherapy. The most common regimens were Platinum/Vinorelbine (38%), Platinum/Taxane (27%) and CAP (15%).The ORR and DCR rates were 12.5% and 56.3% respectively; 6 had partial response, 21 had stable disease, and 21 had progressive disease. The ORR and DCR rates were 20% and 52% for solid and 6.7% and 73.3% for non-solid growth pattern, respectively. The mOS from diagnosis was 7 years (95% CI, 3.5-10.7). The mOS on chemotherapy was 16 months (95% CI, 10.8-24.5). There was a significant difference in mOS between solid and non-solid growth pattern (10.8 v 24.1 months, p=0.015), but not by line of therapy, regimen, or stage at diagnosis. The mPFS on chemotherapy was 4.3 months (95% CI, 2.8-6.3 months). There was a significant difference in mPFS between solid and non-solid growth pattern (4.0 v 7.3 months, p=0.018), but not by line of therapy, regimen, or stage at diagnosis. Conclusions: In this largest to date real-world data on chemotherapy in ACC, response and survival outcomes were lower than historical data. The efficacy of chemotherapy may vary by growth pattern and other patient and tumor factors, which requires further investigation. Given the low ORR and overall slow-growing disease pattern, tumor volumetrics may be better than RECIST to assess treatment benefit.
First-in-human phase 1 trial of the safety, tolerability, pharmacokinetics of BY101298: Initial report from dose escalation cohort.
Authors: Yu Jinming , Sun Yuping , Dang Qi , Zhang Yan , Du Jintong , Wei Yonggang , Ye Fei , Liu Rui , Zhao Qi , Li Zhiyong 
Published: August 2024

e15132 Background: Radiotherapy (RT) is a cornerstone of cancer treatment, leveraging the effect of ionizing radiation to induce DNA damage, primarily through DNA double-strand breaks (DSBs). Non-homologous end joining (NHEJ) stands as the predominant pathway for repairing DSBs, with DNA-dependent protein kinases (DNA-PK) playing a pivotal role in NHEJ pathway. DNA damage repair can compromise tumor cells sensitivity to RT, potentially leading to the development of radiation resistance. BY101298, an innovative and highly selective DNA-PK inhibitor, works to diminish DSBs repair. In synergy with RT or chemotherapy, BY101298 enhances tumor cells eradication, preventing local recurrence and metastasis, thereby improving clinical benefits for cancer patients. Methods: This phase Ⅰa multicenter, open-label, dose-escalation study assessed the safety, tolerability, and clinical efficacy of BY101298. Oral doses ranged from (50 mg to 400 mg once/day [QD]) in continuous 28-day cycles. Primary outcome was safety and tolerability; secondary outcome was PK; exploratory outcome was DNA-PK phosphorylation (PD). Adverse events (AEs) were monitored per the Common Terminology Criteria for Adverse Events (CTCAE version5.0). Responses were assessed every other cycle using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Results: Data from 9 pts with advanced solid tumors (cutoff: 26 December 2023; 2 men, 7 women; median age 58.0) revealed a linear increase in BY101298 AUC exposure and Cmax with dose escalation. Daily dosing for 15 consecutive days showed no AUC increase. Serum drug concentration correlated significantly with DNA-PK phosphorylation. All pts, previously systemic treated, received doses of 50 mg QD (n = 2), 100 mg QD (n = 3), and 200 mg QD (n = 4). Median treatment duration was 30 days (range: 1-57), with one patient (11.1%) continuing. Median relative dose intensity was 100%. Common treatment-related AEs (≥25%), primarily grade 1, included hypoalbuminemia (n = 5, 55.56%); anemia (n = 4, 44.44%); nausea (n = 3, 33.33%); weight decreased (n = 3, 33.33%). No pts experienced ≥Gr3 AEs. Two pts experienced serious AEs (none of which were considered treatment-related). No treatment discontinuations, dose reductions, or deaths attributed to treatment-related. The final dose group, representing the fourth cohort, is scheduled to commence shortly and is expected to conclude in April as per our estimation. Conclusions: In pts with advanced solid tumors, BY101298 exhibits a favorable safety profile and manageable toxicity. Vomiting was noted as a potential risk associated with BY101298. Further studies are imperative to elucidate the efficacy of BY101298 in combination with radiotherapy among pts with advanced solid tumors. Research Sponsor: This study received support from Chengdu Baiyu Pharmaceutical Co., Ltd. Clinical trial information: CTR20230997.