bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNS efficacy of trastuzumab deruxtecan in metastatic breast cancer: A single-institution, real-world analysis.
Authors: Zhang XiaojiE , Yeung Kay T. 
Published: July 2024

e13117 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that revolutionized the management of patients with HER2+ (HER2 FISH+, IHC 3+) and HER2low (HER2 FISH-, IHC 1+/2+) metastatic breast cancer (MBC). Studies have shown that T-DXd may induce antitumor activity in HER2+ MBC with brain metastases (BM). However, data is limited on the central nervous system (CNS) efficacy of T-DXd in HER2low disease. The only report thus far is from the HER2low cohorts in the DEBBRAH study with 12 patients showing an intracranial overall response rate (ORR-IC) of 50% and progression free survival (PFS) of 5.7 months. Here, we provide a real-world, retrospective analysis of the CNS efficacy of T-DXd in HER2+, HER2low, and HER2null MBC with BM. Methods: This is a single institution, retrospective analysis of patients with MBC with BM who received T-DXd between January 2020 and November 2023. Patients with HER2+, HER2low, or HER2null MBC and BM, treated or untreated at the time of T-DXd initiation, were included. All patients had baseline brain magnetic resonance imaging before T-DXd initiation. Efficacy analyses were performed using the RECIST 1.1 criteria to CNS target lesions by investigator assessment. ORR-IC and intracranial clinical benefit rate (CBR-IC) were reported. CNS PFS, defined as time until CNS progression or death of any cause, and overall survival (OS) were also evaluated. Results: 29 patients were included in the study: 10 (35%) had HER2+, 16 (55%) had HER2low, and 3 (10%) had HER2null disease. The patients had ECOG performance status ranging from 0 to 3, and received a median of 3 prior lines of therapy (range 1-8). At baseline, 3 patients (10%) had untreated BM, 6 (21%) had prior surgery, and 23 (79%) had prior radiation. 28 (97%) had concurrent extra-cranial metastases. Best CNS response and duration of response are listed in the table below. ORR-IC was 10% overall and 6% in HER2low group. CBR-IC was 58% overall and 50% in HER2low group. Median OS in all patients was 65 weeks. Median CNS PFS was not statistically different in the overall group (24 weeks) compared to the HER2low group (21 weeks) with p=0.4661 via log rank test. Conclusions: This is the first real-world study reporting the CNS efficacy of T-DXd in patients with MBC across HER2 expression levels. The CNS efficacy of T-DXd in our institutional experience was similar in HER2+ and HER2low MBC, and was much lower than previously reported in prospective clinical trials. Performance status, extent of prior treatment, and systemic disease burden likely contributed to this difference. Larger cohort and prospective studies on patients with HER2low MBC with BM are warranted. [Table: see text]
A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.
Authors: Wang Feng , Xia Jin , Meng Xiangrui , Ji Yinghua , Yang Xiuli , Hong Yong-Gui , Wang Junsheng , Cui Donghai , Luo Zhiquan 
Published: July 2024

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.
Impact of positive tumor-informed margin and TP53 mutations on surgical outcomes in esophageal squamous cell carcinoma.
Authors: Lu Di , Tong Yu , Liu Jingwen , Chen Zhiming , Wang Zhizhi , He Chunhong , Li Shaobin , Mai Shijie , Rao Xuguang , Cai Kaican 
Published: July 2024

e16024 Background: The complete removal of esophageal squamous cell carcinoma (ESCC) with clear margins (R0 resection) is pivotal for patient prognosis. However, it is limited by the potential inaccuracies of conventional histopathology. Next-generation sequencing (NGS) for minimal residual disease (MRD) detection might improve the prediction of postoperative outcomes. Methods: The study cohort included a total of 48 operable ESCC patients, from whom resected esophageal tumors, resection margins, and normal tissues were collected and profiled by a 425-gene panel. Comparisons of mutational features were conducted across various tissue types, and their associations with disease-free survival (DFS) were explored. Results: Mutations were detected in 81.8% (27/33) of normal tissues, 95.8% (46/48) of tumors, and 50.0% (24/48) of resection margins. In general, genetic alterations in resection margins closely resembled those in tumor tissues, but were distinct from normal tissues. Both tumor and margin samples showed higher variant allele frequencies (VAFs) and fewer mutations per patient than normal samples ( p < 0.0001). Moreover, eight patients exhibited identical mutations in paired margin and tumor samples. Notably, one patient out of eight with the same TP53 p.T175H mutation across all sample types exhibited the shortest DFS of only two months. Mutations in TP53 and NOTCH1 were the most common, displaying unique mutational patterns among different sample types. While NOTCH1 mutations were detected more frequently in normal tissues ( p = 0.001), TP53 mutations were enriched in tumors ( p = 0.04). Furthermore, normal tissues exhibited a distinct pattern of mutation sites for TP53 and NOTCH1 compared to those observed in tumor or margin tissues. We characterized tumor-informed margin (TiM) by the presence of identical mutations in both tumor and adjacent margins. The positive TiM status was associated with a shorter DFS, particularly when considering TP53 mutations alone ( p = 0.022) or excluding NOTCH1 mutations ( p = 0.031). Conclusions: A positive TiM status with TP53 mutations is a promising biomarker indicating poor surgical outcomes in ESCC. Mutations within NOTCH1 are common but showed no association with DFS. These findings provide novel insights into the feasibility of genetic profiling of resection margins to facilitate optimizing postoperative therapeutic regimens for ESCC.
A single-arm, multicenter, phase II study of utidelone in advanced solid tumors: Efficacy data from screening and the expansion cohort assessing utidelone plus sintilimab and oxaliplatin for advanced gastric cancer.
Authors: Sun Meili , Yao Herui , Zhou Ying , Chen Hua , Fan Qingxia , Jiang Hua , Wang Shubin , Wu Yumei , Zhao Rui , Tang Li , Li Jin 
Published: July 2024

e16055 Background: Treatment regimens for many advanced solid tumors are limited and alternative options are needed.Utidelone is approved for the treatment of advanced breast cancer in China. NCT04911907 is a single-arm, multicenter, phase II study to assess the efficacy and safety of utidelone in advanced cancer. Stage I of the trial, completed in October 2023, included patients (pts) with pretreated advanced solid tumors. Based on the stage I data, a stage II expansion cohort (USO-G) investigated utidelone plus sintilimab and oxaliplatin as first-line therapy for advanced gastric cancer (GC). Here, we report efficacy and safety data from stage I and stage II for interim analysis. Methods: Eligible pts aged 18–70 years with pretreated advanced solid tumors were enrolled in stage I and received utidelone monotherapy (35 mg/m2/day iv on days 1–5 every 21 days). In stage II, eligible pts with metastatic and/or unresectable HER2 negative GC received utidelone (30mg/m2/day iv on days 1–5 every 21 days) plus sintilimab (200 mg iv Q3W) and oxaliplatin (130 mg/m2/day Q3W for up to 6 cycles), until disease progression or unacceptable toxicity. Results: From March 18th 2021 to October 13th 2022, 79 pts were enrolled into 7 tumor cohorts and 54 pts were evaluable for efficacy. The best overall responses were 1 CR, 3 PRs and 3 SDs in 10 esophageal cancer pts, 3 PRs and 5 SDs in 15 GC pts, 1 PR and 3 SDs in 10 ovarian cancer pts, SD for all 4 cholangiocarcinoma pts, 3 SDs in 4 cervical cancer pts, 2 SDs in 3 pancreatic cancer pts and a PR in 1 neuroectodermal tumor patient. Grade 3/4 TRAEs occurred in 27.8% of pts in stage I, and included anemia (13.9%), peripheral neuropathy (11.4%) and neutropenia (7.6%). No treatment-related deaths occurred. Gastric cancer was chosen as the expansion cohort indication. As of February 1st 2024, 14 eligible pts with GC with a median age of 57 years (range, 41–69) were enrolled. The median follow-up was 5.5 months (range, 1.0–9.7) and the longest duration of response was 8.0 months. A total of 8 PRs and 3 SDs were achieved in the 11 pts evaluable for efficacy, and 6 pts including the 3 with SD were still receiving treatment. Grade 3/4 TRAEs occurred in 28.6% of pts including diarrhea (14.3%), fatigue (14.3%), neutropenia (14.3%), and vomiting (7.1%). Other AEs were all Grade 1 or 2, with no treatment-related deaths. Conclusions: Utidelone monotherapy showed antitumor activity and manageable toxicity in pts with advanced solid tumors. Utidelone plus sintilimab and oxaliplatin demonstrated promising efficacy and an acceptable safety profile as first-line treatment for pts with GC. Stage II of the USO-G study is still actively enrolling; further data will be provided at the time of presentation. Clinical trial information: NCT04911907 .
Analysis of the value of chromosomal instability test for evaluating early efficacy assessment in advanced gastric cancer.
Authors: Luo Xinpei , Yuan Min , Liu Zhuqing , Xie Rongjia , Xu Qing 
Published: July 2024

e16060 Background: Gastric Cancer is featured by frequent somatic copy number alterations (SCNA) and high chromosomal instability (CIN). Circulating tumor DNA (ctDNA) is a minimally invasive approach, effective for the real-time follow-up of cancer. However, the clinical significance in gastric cancer is not yet determined.We performed this study to to evaluate whether ctDNA-based CIN analysis can predict treatment efficacy in advanced gastric cancer (AGC). Methods: The patients with surgery or cytopathology confirmed AGC and who received chemotherapy were enrolled. The blood sample (10ml) for ctDNA sequencing were obtained at baseline (BL) (before first-line chemotherapy) and at the time of efficacy assessment, respectively.The ctDNA of gastric cancer patients was isolated from plasma using QIAseq ctDNA extraction kit (Qiagen), and then repaired and amplified. The whole genome data were analyzed for DNA copy number abnormality, which was expressed as TFx value, and TFx ≥ 0.06% was taken as the positive value of chromosomal instability.Clinical responses (by RECIST 1.1 criteria) were estimated at the time points after 2 cycles of treatment. Results: A total of 18 patients were registered.There were 12 males and 6 females with a median age of 64 years (range 43-72 years).According to the RECIST1.1 criteria, there were 7cases of PR, 9 cases of SD, and 1 case of PD after treatment,1 case was under observation. Patients with CR+PR+SD were defined as the treatment-effective group, and with PD were defined as the treatment-ineffective group.The treatment-effective group mean value of CIN TFx value before treatment was 3.47±7.69, after treatment was 0.59±1.46(P<0.05),14 (82.35%) of these patients experienced a decrease in TFx values after treatment.Patients in the treatment-naïve group showed elevated TFx values.We divided the patients into group A and group B,group A was defined as the TFx value did not fall into the normal range after treatment, and group B was defined as the TFx value fell into the normal range and was called the rapid clearance group.Comparing the efficacy to the CIN group, 71.4% of patients with PR showed rapid clearance of ctDNA, while no clearance of ctDNA was observed in patients with PD,50.0% of patients with SD showed rapid clearance of ctDNA. Rapid clearance of ctDNA was also associated with longer survival, with a median OS of 7.2 months in group A and 17.85 months in group B, with HR of 0.55 (95% CI: 0.081-3.775 P > 0.05) However, there was no significant difference, probably due to too little data.In terms of PFS, Group B did not demonstrate benefit, with a median PFS of 5.9 months in Group A compared to only 3.9 months in Group B (P = 0.647). Conclusions: Dynamic ctDNA-based CIN assay can be used as a biomarker for efficacy assessment in metastatic gastric cancer. Rapid clearance of ctDNA is associated with longer survival, but this still needs to be validated with extensive data.
Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.
Authors: Chen Yicong , Yu Ruixuan , Zhou Xiaojuan , Zeng Xiaoxiao , Xu Yong , Peng Feng , Zou Bingwen , Zhou Lin , Gong Youling , Wang Jin , Wang Yongsheng , Huang Meijuan , Lu You , Liu Yongmei 
Published: July 2024

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P < 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.
Homologous recombination deficiency score served as an independent prognosis factor in esophageal squamous cell carcinoma.
Authors: Wang Yulu , Ding Bowen , Tao Yunlan , Huang Lingli , Zhu Qian , Gao Chengying , Feng Mingli , Han Yuchen 
Published: July 2024

e16080 Background: Homologous recombination deficiency (HRD) is a functional impairment of the homologous recombination repair (HRR) pathway, pivotal for mending DNA double-strand breaks, contributing significantly to cancer-associated genomic instability. While BRCA mutations traditionally underlie HRR defects, recent studies highlight varied responses to poly (ADP-ribose) polymerase (PARP) inhibitors based on specific HRR-related gene alterations. Despite HRD's relevance in various cancers, its role in esophageal squamous cell carcinoma (ESCC) remains underexplored. Methods: We conducted a retrospective analysis of HRD scores in 96 ESCC patients, assessing correlations with clinical characteristics and survival outcomes. Genomic sequencing was performed using a customized superHRD NGS panel. HRD scores were calculated based on 54,000 single-nucleotide polymorphisms, employing Kruskal-Wallis ranksum tests and two cut-off points for quantitative analysis. Kaplan-Meier survival and Cox regression model were employed to evaluate disease-free survival (DFS) and overall survival (OS). Results: Higher HRD scores correlated with advanced tumor stages, recurrence, and specific gene mutations ( TP53 and ABCB1). APC mutations were associated with lower HRD scores. Patients with high HRD scores demonstrated significantly shorter disease-free survival (DFS) and a trend towards shorter overall survival (OS), especially those who did not receive adjuvant therapy, emphasizing HRD's prognostic value. Conversely, HRD-high patients undergoing adjuvant therapy showed a tendency towards extended OS. Multivariate analysis identified HRD as an independent prognostic factor (HR = 2.814 for recurrence, HR = 1.772 for death). Validation with The Cancer Genome Atlas (TCGA) ESCC dataset supported our findings. Conclusions: This study unveils associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, emphasizing HRD's potential as a prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies. Future investigations should explore underlying molecular mechanisms and therapeutic implications of HRD-associated pathways in ESCC management.
Social factors in the receipt of treatment for locally advanced esophageal cancer.
Authors: Ricker Ansley Beth , Robinson Jordan , Shea Reilly , Cockerham Katelyn , Simpson Matigan , Squires Malcolm Hart , Salo Jonathan C. 
Published: July 2024

e16093 Background: Treatment for locally advanced esophageal cancer consists of chemoradiation (chemoRT) followed by esophagectomy. Studies have suggested Black patients were less likely to undergo surgery for esophageal cancer with inferior survival rates, attributing this to differences in access to surgery. These studies have not always accounted for differences in the natural history of adenocarcinoma and squamous cell carcinoma, which have strong racial correlations and different rates of surgical resection. The current study examined outcomes and patterns of care for patients with locally advanced esophageal cancer, both adenocarcinoma and squamous cell carcinoma, in relation to their sociodemographic characteristics. Methods: Patients with clinical stage T2-4, N0-2, and M0 adenocarcinoma or squamous cell carcinoma of the mid or distal esophagus diagnosed between 2010-2021 were included from 11 hospitals across our healthcare system. Treatment decision-points included receipt of chemoRT, unresectable disease after chemoRT defined by metastatic disease or upper mediastinal lymphadenopathy, and receipt of surgery stratified by histology. Age, race, sex, insurance status, socioeconomic status measured by social deprivation index (SDI), and outcome data were collected. Chi-squared test was used for categorical variables and Kruskal-Wallis for continuous variables. Results: 513 patients were included, of whom 472 patients underwent chemoRT (366 adenocarcinoma, 106 squamous cell). Female patients (n =97) were less likely to undergo chemoRT (84% vs. 94%, p = 0.003). Patients without insurance were less likely to undergo chemoRT (86% vs 93%, p = 0.023). After completing chemoRT, 419 patients (82%) were resectable. Surgery was performed in 262/330 patients (79%) with adenocarcinoma and 38/89 patients (43%) with squamous cell carcinoma, reflecting the differences in natural history by histology. Among 330 patients with resectable adenocarcinoma, higher SDI was associated with a lower rate of surgery, while there was no difference in the receipt of surgery based on sex, race or insurance status. There were no detectable social factors associated with receipt of surgery for squamous cell carcinoma. Conclusions: Within our healthcare system, female and Medicaid/uninsured patients are less likely to undergo chemoRT for locally advanced esophageal cancer. Further studies are needed to evaluate whether sex-specific bias plays a role in the receipt of chemoRT. Among patients with resectable locally advanced esophageal adenocarcinoma treated with chemoRT, those with high SDI are less likely to undergo surgery. Further studies are needed to assess which component factors of socioeconomic status most impact the receipt of surgery so they can be targeted. The previous findings that race impacts treatment of locally advanced esophageal cancer are not seen in our healthcare system when accounting for histology.