bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital health program for patients with cancer to support self-management: A retrospective real-world analysis.
Authors: Bjarnadottir Olof K. , Dobies Bartosz , Ísberg Ari Páll , White Alice Jean , Jónasdóttir Sigríður Svala , Oddsson Saemundur 
Published: June 2024

1570 Background: Sidekick Health’s 13-week digital health program was built to support cancer self-management. It was available free of charge to US-based cancer patients through commercial health insurance. The program includes disease education, mindfulness, medication adherence support, and asynchronous messaging with a care manager. We hypothesized that highly engaged users had reduced symptom frequency and severity, and improved quality of life (QoL) outcomes. Methods: In-app data were analyzed for registrations Aug 2021-Jan 2024: n(registered)=1286; n(retained ≥7 days)=795; n(QoL/symptoms)=284. QoL was defined as self-reported sleep quality, energy and stress (10-point scale, ≤4x/week). Symptoms were also self-reported (10-point scale, ≤7x/week). Generalized linear mixed models for repeated measures were used to investigate QoL, symptom frequency and severity changes over the program. Subgroup analysis: weekly iterative k-means clustering into highly- and less-engaged (based on total active days) to mitigate survival bias. Results: Diverse patients from 37 states engaged: mean age 58.0 years (SD=10.5), 71% female; 49% diagnosed <6 months ago, 36% ≥12 months ago; 23% early-stage disease, 26% stable disease, 6% in remission and 2% terminal; 60% received chemotherapy, 24% radiation therapy, and 21% immunotherapy. Most (61%) registered users were active after 7 days and 29% after 90 days. Less-engaged users reported higher mean baseline weight (85.3kg (SD=26.7)) vs highly engaged (76.9kg (SD=18.3); p=0.010) but were otherwise similar (age, gender, height, time since diagnosis and treatment: p>0.05). For QoL, highly engaged users had improved energy (p=0.013) and sleep (p=0.002), but not stress (p=0.164) vs less engaged. A significant time-group interaction for sleep (p<0.001) showed highly engaged users had better sleep, and larger improvements over time vs less-engaged. Overall, users reported fewer symptoms over the program (IRR (95% CI)=0.965 (0.953, 0.978), p<0.001). Symptom frequency decreased significantly for stress (p=0.034) and nausea (p=0.003), but not numbness (p=0.320) or fatigue (p=0.530). Highly engaged users’ symptom severity had a downward trajectory, compared with less-engaged, for fatigue (p=0.044) and nausea (p=0.001), but not stress (p=0.234) or numbness (p=0.680). Conclusions: Theprogram was accessed by a broad patient group and retention was high. Highly engaged users reported improved QoL (energy, sleep) and reduced symptom severity (fatigue, nausea). Total symptom frequency was reduced over the program, as well as for stress and nausea specifically. These findings indicate digital self-management is not only achievable for patients with cancer, but that higher engagement may improve patient-reported outcomes.
Preliminary exploration of Trop2 ADC in combination with immune checkpoint inhibitors in the different molecular subtypes of invasive breast carcinoma.
Authors: Liu Yueping , Jiang Hanxu , Deng Huiyan , Li Jinze , He Jiankun , Liu Xudi 
Published: June 2024

e12558 Background: Human trophoblastic cell surface antigen 2 (Trop2) is a transmembrane protein overexpressed in breast cancer tissues. However, it is present at minimal levels in adult somatic tissues, making it an ideal target for treatment with antibody-drug conjugates (ADCs). Sacituzumab govitecan, an anti-Trop2 ADC, has been approved for the treatment of triple-negative breast cancer and urothelial cancer. Recent studies have demonstrated that human cytotoxic T lymphocytes can recognize Trop2. Accordingly, we aimed to assess the role of Trop2 in the tumor immune activity of different subtypes of breast cancer, and laying the foundation for further studies on the efficacy of the combination of Trop2 ADC and immune checkpoint inhibitors in breast cancer. Methods: We retrospectively retrieved tissues from 152 invasive breast carcinoma of no special type and 111 benign breast tumor tissues and undergoing surgical resection at our institution from 2018 to 2023. Immunohistochemistry was used to detect Trop2 and PD-L1 expression and lymphatic invasion in patients, and their correlations with clinicopathological factors were analyzed. Trop2 expression was evaluated using the H-score. The median as the cut-off value, a score of 0–240 indicated low expression, and 240–300 indicated high expression. Cases with CPS ≥ 1% were considered positive for PD-L1. Results: The expression was Trop2 in breast cancer tissues than in benign tumor tissues (P<0.0001). Immune infiltration analysis suggested that Trop2 expression was correlated with immune cell infiltration and the abundance (P<0.001). Kaplan–Meier plotter analysis demonstrated that high Trop2 expression was related to poor prognosis in patients with triple-negative breast cancer (overall survival: HR=1.53, P=0.029; relapse-free survival: HR=1.26, P=0.045). In contrast, Trop2 expression was not significantly associated with prognosis in other breast cancer subtypes. However, there was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in breast cancer. Conclusions: The findings suggest that Trop2 correlates with poor prognosis and immune cell infiltration in breast cancer. This indicates the role of Trop2 as a potential prognostic biomarker, laying the foundation for further research focusing on the immune regulatory role of Trop2. [Table: see text]
Trastuzumab, pertuzumab and nab-paclitaxel plus pyrotinib or not in neoadjuvant treatment of HER2-positive breast cancer: A multi-center, randomized, open-label, phase II study.
Authors: Chen Xiaosong , Huang Jiahui , Tong Yiwei , Ren Weili , Yu Jing , Gao Weiqi , Zhu Siji , Hong Jin , Wu Jiayi , Huang Ou , He Jianrong , Chen Weiguo , Li Yafen , Shen Kunwei 
Published: June 2024

e12634 Background: Trastuzumab plus pertuzumab (TP) combined with chemotherapy is the standard neoadjuvant treatment regimen for HER2+ breast cancer. Anti-HER2 tyrosine kinase inhibitor, pyrotinib, shows great efficacy in HER2+ metastatic breast cancer, but lacking efficacy data on the basis of TP and chemotherapy in the neoadjuvant setting. This study aims to evaluate the efficacy and safety of TP plus nab-paclitaxel with or without pyrotinib as neoadjuvant treatment in HER2+ breast cancer. Methods: Stage II-III HER2+ breast cancer patients, stratified by disease stage (II vs. III) and hormone receptor (HR) status (positive vs. negative), were randomized 1:1 into the pyrotinib group or the control group. Both groups received a combination of 3-weekly TP and weekly nab-paclitaxel for 12 weeks. The pyrotinib group was concurrent given 320mg pyrotinib once daily. Primary endpoint was the total pathological complete remission (tpCR), defined as no invasive cancer in the breast and axillary lymph node. Results: From Nov 2020 to Apr 2023, a total of 109 patients were enrolled, with 108 receiving treatment: 55 in the pyrotinib group and 53 in the control group.The tpCR rate was 65.5% (95% CI: 51.4%, 77.8%) in the pyrotinib group, which shows no significant difference with the control group [60.4% (95% CI: 46.0%,73.5), P = 0.585). The breast pathological complete response (bpCR) rates were 70.9% (95% CI: 57.1%,82.4%) and 64.2%(95% CI: 49.8%,76.9%) in the pyrotinib and control group, respectively (P = 0.453). In the pyrotinib group, 52 (94.5%), 31 (56.4%), and 23 (41.8%) patients experienced dose-interruption, dose-reduction, and discontinuation of pyrotinib, respectively. The most common grade ≥3 adverse events in the pyrotinib and control groups were diarrhea (58.1% vs. 0%), decreased neutrophil count (23.6% vs. 15.1%), and decreased white blood cell count (16.4% vs. 7.5%). Conclusions: Our study showed pyrotinib didn’t significantly improve tpCR rate with pyrotinib on the basis of TP and nab-paclitaxel neoadjuvant therapy of HER2+ breast cancer. Concurrent pyrotinib treatment with TP was associated with a high rate of severe diarrhea. Further biomarker analyses are needed to identify which population would receive great benefit with neoadjuvant pyrotinib therapy in HER2+ breast cancer. Clinical trial information: NCT04398914 .
Intracellular retention of TCRαβ/CD3 to generate novel allogeneic CAR-T cells targeting CLL1 for treating acute myelocytic leukemia.
Authors: Li Jun , Liu Kaichun , Xu Guanggui , Chen Shanshan , Zhang Yinhang 
Published: June 2024

e14532 Background: The prognosis of patients with R/R AML is poor and treatment remains challenging. Human C-type lectin-like molecule 1(CLL1) is a type II transmembrane glycoprotein that is highly expressed on AML but is absent on normal HSCs. Clinical studies have shown that autologous CLL-1 is a novel and promising target for the treatment of AML. But autologous CAR-T therapy has been complicated by long production time, high-cost and risks of manufacturing failure, and allogeneic CAR-T cells can overcome these hurdles. Methods: A novel non-gene-editing allogeneic CAR-T platform was developed on the base of intracellular retention of membrane proteins, and named ThisCART (This = TCR and/or HLA-I intracellular sequestered). CLL1-directed ThisCART cells are readily produced with a single lentiviral vector, encoding both a CLL1-targeting CAR and an anti-CD3 single chain antibody with the KDEL peptide fused to its C-termini. The surface expression of CAR and TCRαβ/CD3 was measured by flow cytometer. Specific tumor cytotoxicity was evaluated both in vitro and in vivo. Furthermore, the safety of donor derived ThisCART cells were tested in a xenogeneic GvHD model. Results: The manufacturing platform of CLL1 ThisCART was able to achieve over 150-folds of ex vivo CAR-T expansion in all batches, with the purity of products (CAR-positive/TCRαβ-negative) above 99%. In preclinical models, CLL1 ThisCART did not induce GvHD, and exhibited superior antitumor function compared to benchmark (WO2017091615A) and conventional CLL1 CAR-T cells. CLL1 ThisCART cells were readily produced to a quantity and quality supporting clinical investigation. Conclusions: CLL1 ThisCART cells based on intracellular retention of TCRαβ/CD3 complex demonstrated superior CLL1-dependent cytotoxicity and no xenogeneic GvHD in murine models. With streamlined single-vector-based production, enhanced CAR signaling and potent cytotoxicity and favored preclinical safety profile, CLL1 ThisCART warrant clinical investigation.
Pan-tumor circulating tumor DNA testing in the community oncology setting.
Authors: Raska Paola , Su Zhaohui , Robert Nicholas J 
Published: June 2024

e14556 Background: Circulating tumor DNA (ctDNA) technology allows for monitoring the genomic profile of cancer over time non-invasively, and in a way that is more representative of existing tumor clones than tissue sampling. The clinical and research applications of this new technology are numerous, and they are potentiated through serial ctDNA testing of individual patients. It is important to identify and characterize real-world data sets that will permit the development of both ctDNA’s clinical and research applications. Methods: This is an observational study of breast, non-small cell lung cancer (NSCLC), colorectal and prostate cancer patients who had ctDNA testing in The US Oncology Network from August 2014 to August 2023. All unique ctDNA reports per patient were collected, along with the report dates and patient characteristics. Rate of change in number of unique reports per month through time was evaluated as well as frequencies of serial testing and median time lapse between diagnosis and date of first ctDNA test by cancer type. Results: Number of new unique ctDNA testing reports per month increased for The US Oncology Network from 2014 through 2018 at a rate of 0.86 (95% CI [0.70, 1.02]). From 2018 to 2023 this rate increased to 5.87 (95% CI [5.16, 6.59]) new reports per month. The total number of unique patients with one of the 4 cancer indications and at least one ctDNA test during the study time period was 10,852. The cancer indication with greatest number of patients with ctDNA testing is NSCLC with 5,503 patients, followed by breast with 2,408, and colorectal and prostate with 1,544 and 1,397 respectively. Black patients were equally represented across all 4 cancers at rates of 13.6% for colorectal, 12.7% for breast, and 12% for NSCLC and prostate. Patients over 65 made up 66% for prostate and NSCLC but only 38% and 32% for colorectal and breast respectively. Most patients presented with a single ctDNA test (n = 9482), but an important proportion presented with 2 serial ctDNA tests or more (n = 1370, 12.6%).The median time between either cancer diagnosis date or date of first visit in The Network and the date of the first ctDNA test report was 39 days for NSCLC, 1,690 days for breast, 377 days for colorectal and 772 days for prostate, and presented with a skewed, long right tailed distribution. Median times were similar for Black and White patients across all cancers. Conclusions: The number of patients with ctDNA testing data available is increasing through time without evidence of plateauing. Although the total number of patients represented is still a very small fraction of the total patient population, the rate of increase in number of new reports through time is equivalent to an exponential increase in the total number of reports. 12.6% of patients presented with two tests or more, potentially allowing for pre and post treatment assessments. There’s an opportunity to better align cancer research and cancer treatment paradigms with this new technology.
Novel engineered regulatory macrophages combined with ICIs for post-transplant recurrence after liver transplantation for HCC.
Authors: Hu Yongwei , Zhang Mingshen , He Kaiming , Lv Lei , Yu Haoyuan , Li Siqi , Liu Wei , Li Hua , Yi Shuhong , Yang Yang , Ye Linsen 
Published: June 2024

e14582 Background: Liver transplantation is the most effective treatment for early-stage hepatocellular carcinoma (HCC), but post-transplant recurrence limits the efficacy of surgery and affects the patient prognosis. Most of the current attempts to apply immune checkpoint inhibitors (ICIs) to posttransplant recurrence have resulted in either acute allograft rejection or tumor progression, which may be related to the disruption of the immune balance that maintains immune tolerance and enhances immune activation. Methods: Therefore, we constructed an engineered regulatory macrophages (Mregs) with anti-tumor capacity in the transplant setting using reprogrammed liposomes to precisely regulate the immune microenvironment of post-transplant recurrence, in order to create suitable conditions for the safe use of ICIs. Results: Experimentally, Mregs were shown to prolonged allograft survival without promoting tumor development. Through fusing with the Mregs membrane, reprogrammed liposomes insert an anti-CD47 lipid shell onto the surface, enhancing phagocytosis against tumor. The drug-loaded inner core entered into the cytoplasm to reprogram Mregs. Tomivosertib downregulated the expression of PD-L1 and attenuated the immunosuppressive effect. Pexidartinib inhibited the polarization of the M2 pathway and upregulated the expression of CD80, CD86, and MHC II, enhancing the ability of antigen presentation. Combination with anti-PD-L1 antibodies can enhance anti-tumor effect without accelerating allograft rejection. Both in vivo and in vitro results demonstrate that engineered Mregs provide conditions for the safe use of anti-PD-L1 antibodies in the context of transplantation. Conclusions: Engineered Mregs combined with ICIs enhances immunotherapeutic efficacy and provides a viable therapeutic approach for posttransplant recurrence after liver transplantation for HCC.
PD-1 checkpoint inhibitors related immune-mediated hepatitis in colon cancer: A systematic review and meta-analysis.
Authors: Sanikommu Dhruvi Reddy , Nadeem Ahmed , Uttam Chandani Kanishka 
Published: June 2024

e14615 Background: Immune checkpoint inhibitors have revolutionized the management of advanced colon cancers by targeting programmed death-1 (PD-1) proteins. Along with PD-1, other checkpoint inhibitors PDL-1 and CTL4 have been approved for the treatment of various type of cancers since a decade. However, many immune-related side effects have been associated with them. There is limited data in the literature on PD-1 related hepatotoxicity, mainly immune mediated hepatitis. This systematic review and meta-analysis aim to study the impact of PD-1 checkpoint inhibitors on immune-mediated hepatitis in the context of colon cancer, its incidence among different immunotherapies, risk factors associated with it and exploring treatment modalities. Methods: The study was conducted in accordance with PRISMA guidelines. Multiple databases such as PubMed, EMBASE, Scopus, Cochrane Library and Web of Science from past 10 years were searched up to November 2023. Studies from cohort studies, randomized control trials and case series that have reported on immune-mediated hepatitis in colon cancer patients treated with PD-1 inhibitors were included. Results: Overall pooled incidence of immune mediated hepatitis was between 1% -5% with an average of 4.1% (95% CI, 2.8-5.8) among patients with advanced colon cancer treated with PD-1 inhibitors. Among different inhibitors, incidence was lowest with Pembrolizumab, around 1.4%; and highest with Cemiplimab with 5.1%. This is crucial in optimizing treatment for advanced colon cancers. The meta-analysis also found risk factors of male gender, older age and pre-existing liver-conditions (Hepatitis B and C), contributing to the development of hepatitis. Subgroup analysis will be performed to explore potential differences in incidence rates based on patient characteristics, dosages of medications, duration of treatment and concomitant medications. Other objectives include determining the timeline and grades of toxicity. Conclusions: By incorporating data from other studies and understating safety profiles, the findings will highlight the need for close surveillance for toxicity monitoring. This would also provide insight for clinical providers to make informed decisions regarding treatment selection. Toxicities are noted to be under-reported; hence we urge clinicians to report such immune toxicities. Further research is needed to elucidate underlying mechanisms to develop strategies for mitigating adverse events.
Comparison of pembrolizumab plus chemotherapy versus concurrent or sequential radiochemotherapy in patients with driver mutation-lacking lung adenocarcinoma presenting with recurrent laryngeal nerve invasion leading to hoarseness.
Authors: Lu Zhuming , Xu Shengshan , Ye Min , Shen Tao , Zhang Xin , Rao Dongping , Chen Jiarong , Lin Zhichao , Chang Mingzhang , Xiong Guoping , Li Ronggang , Wang Zhihui 
Published: June 2024

e14635 Background: For patients with advanced non-small cell lung cancer (NSCLC), particularly those with adenocarcinoma lacking a driver mutation, the encroachment upon the recurrent laryngeal nerve causing hoarseness presents a substantial challenge in treatment. Such patients, at TNM stage IIIB or higher, may undergo platinum-based doublet chemotherapy combined with concurrent or sequential radiotherapy. Despite these treatments, survival rates remain modest, and quality of life is significantly impaired by symptoms such as hoarseness, dysphagia, and coughing. Recently, pembrolizumab combined with chemotherapy has emerged as a frontline treatment for adenocarcinoma patients, showing promising outcomes in unresectable, advanced stages of the disease. However, its efficacy in patients experiencing hoarseness due to recurrent laryngeal nerve involvement has not been previously investigated. Methods: Between September 2018 and October 2022, Jiangmen Central Hospital admitted 71 patients with advanced adenocarcinoma and hoarseness, who lacked a driver mutation as confirmed by NGS testing. After excluding patients who did not complete the treatment plan, the remaining subjects were randomly divided into two groups. The treatment group, consisting of 21 patients, received pembrolizumab, pemetrexed, and platinum-based doublet chemotherapy. The control group, also comprising 21 patients, underwent concurrent or sequential radiotherapy alongside pemetrexed and platinum-based chemotherapy. Results: Among the treatment group, hoarseness was reversed in 13 out of 21 patients, with a return to normal vocal function. In the control group, 5 out of 21 patients experienced a reversal of hoarseness. The treatment group showed superior outcomes in reversing hoarseness caused by recurrent laryngeal nerve involvement (p=0.013). The objective response rate (ORR) in the treatment group was 28.57%, with a disease control rate (DCR) of 66.67%. In contrast, the control group had an ORR of 9.52% and a DCR of 28.57% (p<0.05). The Progression-Free Survival (PFS), as calculated by the Kaplan-Meier survival curve method, was 11.77 months (95% CI: 11.19-12.35) in the treatment group and 7.53 months (95% CI: 6.73-8.33) in the control group, indicating a significantly higher survival rate in the treatment group (p<0.05). Conclusions: In patients with advanced lung adenocarcinoma, pembrolizumab combined with chemotherapy appears to effectively reverse hoarseness caused by recurrent laryngeal nerve involvement, higher objective response rates, and increased PFS. This suggests the necessity for multicentric, prospective, evidence-based studies in the treatment of lung adenocarcinoma patients with hoarseness due to recurrent laryngeal nerve invasion.