bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and economic cost in common primary cancer admitted with COVID-19: Analysis of NIS 2020.
Authors: Suenghataiphorn Thanathip , Wattanachayakul Phuuwadith , Srikulmontri Thitiphan , Kulthamrongsri Narathorn , Xanthavanij Nutchapon , Tribuddharat Narisara , Buasri Kochakorn , Danpanichkul Pojsakorn , Saowapa Sakditad , Lohawatcharagul Tuntanut , Osataphan Soravis Alm 
Published: August 2024

182 Background: Recent data showed the detrimental effects of COVID-19 infection on various conditions, resulting in a wide range of health disparities and worsening outcomes, as well as an increased burden of cost. However, limited information exists on the impacts of COVID-19 infection on the most commonly admitted with primary cancer, regarding clinical and economic impact. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted with the most common admitted with primary cancer, using relevant ICD-10 CM codes. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including the cost of hospitalization and length of stay. Statistical significance was established at a p-value of 0.05. Results: We estimated 919,104 hospitalizations with a primary discharge diagnosis of cancer conditions. Of these, 0.54% (4,985/919,104) had a concurrent diagnosis of COVID-19 infection and 46.1% were female. The mean age was 63.6 years old and Caucasians dominated the majority of the records (69.7%), followed by Hispanics (13.1%). In a multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality for all cancer conditions and other outcome. The txable denotes all-type and subpopulation analysis. Conclusions: In conclusion, our study encompasses all most common admitted primary cancer conditions and shed light how COVID-19 infection is associated with higher in-hospital mortality, prolonged hospital stays, and increased economic burden in various condition. Future longitudinal studies are warranted to comprehensively assess the long-term health sequelae in this population. [Table: see text]
Delayed addition of PD-1/PD-L1 inhibitors into chemotherapy on the outcomes for patients with extensive-stage small cell lung cancer: A propensity score-matched study.
Authors: Lu Shuangqing , Tian Yaru , Zhu Hui 
Published: August 2024

208 Background: Immunotherapy in combination with chemotherapy has become the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, some patients failed to undergo simultaneous immunotherapy at the time of initial chemotherapy, and whether this will have an impact on the efficacy of immunochemotherapy has not been fully explored. Methods: Between January 2020 and December 2022, the study included 416 patients diagnosed with ES-SCLC and receiving first-line immunotherapy, divided into two groups: delayed-IO (administering PD-1/PD-L1 inhibitors at 2-4 Cycles of chemotherapy) and early-IO (administering PD-1/PD-L1 inhibitors concurrent with first-cycle chemotherapy). Propensity score matching (PSM, 1:1) was performed to balance the baseline characteristics of the two groups. The primary endpoints were OS and PFS. Calculations were performed using the Kaplan-Meier method and comparisons were made using the log-rank test. Results: Mainly due to the fact that PD-L1/PD-1 inhibitors were not included in the medical insurance, which was difficult for patients to afford and the poor physical condition of some patients, taking into account the safety of the patients themselves, 72 patients in the delayed-IO group (2 cycles of chemotherapy: 41; 3 cycles: 16; 4 cycles: 15), and 344patients were included in the early-IO group. The median OS and PFS were 24.00 months and 8.75 months in the delayed-IO group, and those were 18.59 months and 7.57 months in the early-IO group, respectively, before PSM. There was no significant difference in OS and PFS between the two groups (HR 0.72; P = 0.054 and HR 0.86; P = 0.281, respectively). After PSM, there were 72 patients in each of the two groups. The median OS in the delayed-IO group and the early-IO group was 24.00 months and 18.79 months, respectively (HR 0.60, 95% CI 0.38-0.97; P = 0.037). Median PFS was 8.75 and 6.49 months in the two groups, respectively (HR 0.69, 95% CI 0.48-0.99; P = 0.044). There was a statistically significant difference between the two groups. The overall adverse event profile was comparable between the two groups. Conclusions: Our findings suggest that administering PD-1/PD-L1 inhibitors at 2-4 Cycles of chemotherapy was superior to administering PD-1/PD-L1 inhibitors concurrent with first-cycle chemotherapy in patients with ES-SCLC, while the safety profile of both was similar.
Long-term survival after metasectomy in patients with bone or soft-tissue metastases from renal cell carcinoma.
Authors: Higuchi Takashi , Miwa Shinji , Hayashi Katsuhiro , Yamamoto Norio , Tsuchiya Hiroyuki 
Published: August 2024

227 Background: Renal cell carcinoma (RCC) is reported to be associated with long-term survival, and surgical resection is now recommended in patients with metastatic lesions. This study evaluated the long-term outcome of surgery for bone or soft tissue metastases from RCC. Methods: Between 1993 and 2014, 58 patients (46 men and 12 women) underwent surgery, excluding palliative surgery, for bone or soft tissue metastatic lesions from RCC at our institution. These patients were retrospectively evaluated for factors associated with prognosis by using the log-rank test and Cox proportional hazards analysis. Results: The patients’ mean age was 60 years, and the mean follow-up period was 52 months. The surgical sites included the spine (33 patients), limb bone (10 patients), pelvis (8 patients), thoracic bone (4 patients), and soft tissue (3). The surgical procedures were total en bloc spondylectomy (TES) in 33 patients, wide excision in 13 (6 of them were also treated with prosthesis), and curettage and bone grafts in 12 (4 of them were treated with internal fixation). The 3-, 5-, 10-, and 15-year overall survival (OS) rates were 75%, 62%, 48%, and 25%, respectively. According to the surgical methods, the 5-year OS was 64% for TES, 62% for wide excision, and 46% for curettage and bone grafts. According to the surgical site, the median survival time was 127 months for the spine, 140 months for the limb bone, and 54 months for the pelvis. In multivariate analysis, preoperative lung metastasis and the pathological type, except for clear cell carcinoma, were independent risk factors for poor prognosis. However, age, performance status, Motzer classification, and abnormal blood test results were not significant risk factors. Conclusions: Our findings suggest that the surgical resection of bone and soft tissue metastatic lesions from RCC is a favorable option for improving prognosis even in patients with unfavorable conditions such as an advanced age or poor performance status. Now that treatment outcomes for renal cell carcinoma are improving, bone metastases can be treated with surgery.
Non-invasive minimal residual disease detection of liver cancer using circulating tumor DNA features and α-fetoprotein: A prospective study.
Authors: Chang Yinyin , Ren Qingqi , Li Shiyong , Zhang Liangliang , Feng Yumin , Long Guanghui , Mao Mao 
Published: August 2024

229 Background: Liver cancer hasahigh recurrence rate of 50%-70% for early-stage patients. Minimal residual disease (MRD) is closely correlated with cancer early recurrence. Here, we developed SeekInCure, a non-invasive assay to detect MRD and predict the prognosis of liver cancer patients after radical surgery. Methods: 32 liver cancer patients undergoing radical surgery were prospectively enrolled. 8 mL peripheral blood was collected from each patient before and after surgery, respectively. SeekInCure assay, which integrated the protein tumor marker (AFP) and cancer genomic hallmarks: copy number aberration, and fragment size from ctDNA to calculate a score (PHCC), was utilized to detect the cancer signal in each blood sample. MRD status determined by PHCC value was correlated with the clinical outcome (OS) and the benefit of treatment after radical surgery. Results: Out of the 32 liver cancer patients, 78.1% (25/32) were at early stages (Stages I/II: 65.6%/12.5%), and 59.4% (19/32) received systemic treatment after surgery. MTB- patients (12.5%, 4/32) showed better overall survival (OS) than MTB+ patients (87.4%, 28/32) with a high hazard ratio (HR) value of 1.19. After radical surgery, 23 HCC patients were MRD-, including 4 MTB- patients remaining negative; meanwhile, 9 out of 28 MTB+ patients remained MRD+. The OS of MRD- patients was significantly better than that of MRD+ patients (HR 5.67; 95% confidence interval (CI), 1.33 ~ 24.20; P = 0.008). Moreover, the OS of MRD- patients with and without systemic treatment showed no significant difference (P = 0.930). Conclusions: This prospective study demonstrated the potential clinical value of ctDNA in detecting MRD status to predict the prognosis in early-stage liver cancer patients and to identify patients who may benefit from avoiding overtreatment. This strategy requires validation in independent prospective studies.
Examining molecular landscape and drug sensitivity profiles of patient-derived xenografts from resected brain metastases.
Authors: Morikawa Aki , Rastogi Tusharika , Ulintz Peter , Serhan Habib , Nieblas-Bedolla Edwin , Heth Jason , Cheng Xu , Bao Liwei , Udager Aaron M. , Soellner Matthew , Merrill Nathan , Merajver Sofia Diana 
Published: August 2024

28 Background: Brain metastases (BrMet) remain an unmet need. Preclinical models of BrMet are rare but can be a valuable tool to interrogate pathology and develop novel therapeutic approaches. We previously published molecular profiles and drug sensitivity screening using novel BrMet patient-derived xenograft (PDX) models established from resected BrMet from patients with breast cancer. We further expanded our study to include BrMet from other solid tumors. Methods: We ascertained the genomic profiles of thirteen novel non-breast BrMet PDX models from patients undergoing clinically indicated surgical resection of BrMet. We then conducted drug sensitivity screening on ex vivo organoids with a panel of over 350 drugs to interrogate drug responses. We also collected information on molecular alterations and clinical treatment history from matched source patient material to correlate molecular alterations between tissue and matched PDXs when available, as well as with drug response in PDXs. Results: The PDXs included tumors that commonly (lung and melanoma) and less commonly (ovarian and sarcoma) metastasize to the brain. We observed potentially targetable DNA alterations in the DNA damaging repair pathway ( ATM, BRCA, CHEK2) and ERBB2. Using the drug sensitivity score 3 (DSS3), we assessed the sensitivity of the drugs tested. While the panel did not include the recently approved anti-HER2 targeted drugs, lapatinib (anti-HER2 TKI), and PARP inhibitors, e.g. olaparib and niraparib, were inactive against these PDXs. The three most active drugs among the BrMet PDXs were romidepsin, bortezomib, and triptolide, similar to what we observed previously for breast BrMet PDXs. When available, we correlated the DSS3 from the PDX testing with the drug exposure history and potentially actionable alterations reported in the matched source patient clinical samples. Interestingly, one case with CDKN2A/1B homozygous deletion had differential sensitivity against CDK inhibitors (highly active to dinaciclib but inactive to abemaciclib and palbociclib). Conclusions: We observed prevalent gene alterations associated with homologous recombination deficiency and HER2 among these non-breast BrMet PDX models, opening an opportunity for novel cross cancer approaches as these alterations are also reportedly linked to BrMet from breast cancer, these mechanisms may contribute to the propensity for BrMet. We also found that there are common drugs that are active across BrMet from different solid tumor types. To further explore the shared molecular features of BrMet across various solid tumors, we have established additional PDX models (near 100) from multiple solid tumors and plan to report on the molecular features.
Hypoxia-responsive synthetic gene circuits to improve safety and potency of CAR T cell therapy for solid tumors.
Authors: Schreiber Yannick , Leonard Joshua 
Published: August 2024

37 Background: Engineered cell therapies expressing a chimeric antigen receptor (CAR) in human T cells have demonstrated great promise for the treatment of hematological malignancies. However, unique challenges remain in translating the success of CAR T cell therapies to solid tumors, namely: (1) specificity: there are few truly unique antigens present on solid tumors, leading to off-target effects that damage normal tissue and pose safety risks; and (2) suppression: solid tumors develop microenvironments that are immunosuppressive and decrease T cell survival and tumor-directed cytotoxicity. To address these challenges and improve the safety and potency of solid tumor cell therapy, we engineered cells with synthetic genetic circuits containing a previously validated hypoxia biosensor (HBS) that responds to upregulation of the native HIF1α and HIF2α transcription factors by hypoxia, enabling the cells to sense and respond to the hypoxic tumor microenvironment ubiquitous among solid tumors. Methods: We evaluated CAR expression from circuit architectures containing the HBS promoter driving expression of both CAR and native HIF1α, HIF2α, as well as from circuit architectures containing the HBS promoter and our toolkit of synthetic transcription factors and promoters. Circuits were integrated into HEK293 cells via PiggyBac transposon vector to generate stable cell lines. Cells were subsequently cultured in normoxia (21% O2) and hypoxia (1% O2), and harvested for flow cytometric analysis to evaluate CAR surface expression across a three day time frame. Results: We identified novel circuits providing fast reporter output with minimal background signal under hypoxic conditions, and elucidated design rules that enable or restrict amplification of transgene in native HIF1α and HIF2α-containing circuits. We observed differences in CAR transgene expression in hypoxia between circuits containing HIF1α and HIF2α-mediated feedback, suggesting mechanistic differences in regulation of HIF1α and HIF2α when overexpressed. Additionally, we observed greatly amplified transgene expression in circuit topologies containing feedback mediated by our synthetic transcription factor and promoter toolkit compared to native HIF1α and HIF2α-containing circuits and cells constitutively expressing CAR. Conclusions: We present a new therapeutic technology that senses hypoxic environments and enables high-output sense and respond behaviors with therapeutic outputs. We envision that this technology will enable development of safer, more effective cell therapies for solid tumors, as well as provide new biological and mechanistic insights that can inform the future development of hypoxia-responsive cell therapies.
Evaluating interaction between tumor educated platelets and cancer stem cells on breast cancer subtypes.
Authors: Guha Aishwarya , Sultana Jasmine , Bhuniya Avishek , Chakravarti Mohona , Bera Saurav , Sarkar Anirban , Dhar Sukanya , Das Juhina , Ganguly Nilanjan , Das Tapasi , Alam Neyaz , Ghosh Indranil , Hajra Srabanti , Bose Anamika , Baral Rathindranath , Banerjee Saptak 
Published: August 2024

5 Background: Thrombocytosis has been reported to be responsible for poor prognosis of numerous malignancies. This swarm of platelets acts as foe for the body but as mate for the cancer cells by providing a protective shield around them, helping them to escape immunosurveillance process. A bidirectional interaction between platelets and tumor cells promote their conversion to an activated tumor educated platelet (TEP) state. The present report reveals the critical role played by TEPs to promote metastasis in BC subtypes by interacting with cancer stem cells (CSCs). Methods: Status of intra-tumoral and humoral TEPs (CD41+/CD62P+) was screened in luminal A (LumA) and triple negative (TNBC) BC subgroups. The impact of TEPs on lin-/CD44+/CD24- CSCs of both the categories in-vitro, was deciphered by performing mammosphere assay, clonogeneic and migration assays, with final validation in murine system. Effect on various genes and proteins related to stemness, metastasis and angiogenesis as a result of this interaction was elucidated by RT-PCR, flow cytometry and western blotting. Results: High percentage of TEPs in the peripheral blood is a potential biomarker and responsible for poor prognosis in BC subtypes. Both Lum A and TNBC patients had elevated TEP frequency, compared to healthy blood. Further, patients in the pre-carcinogenic stage had platelet count of >3.5 lakhs. Additionally, screening of breast tumor sections revealed intra-tumoral enrichment of TEPs, comparatively to a greater extent in TNBC than LumA, supporting their role in disease aggression. Also, a positive correlation was noted between TEP and CSC frequencies proving their synergistic interactions. Moreover, in-vitro, TEP influenced CSCs exhibited enormous clonogenic and tumorigenic potentialities. Their metastatic nature was confirmed by their enhanced migratory, invasive, angiogenic capacities with higher VIMENTIN and TWIST along with HIF1α, CD31 and MMP9 expression compared to E-CADHERIN. In line with in-vitro observations, in-vivo too, TEP~CSC produced metastatic colonies in murine lungs. Upon investigation, it was disclosed that it is through WNT-βcatenin-VEGFR2 axis that this mutual interdependency was functioning. Conclusions: This study advocates for the importance of TEPs as potential biomarker in BC diagnosis. Their alliance with vicious CSCs to promote disease advancement acquiesce them as a novel restorative agent.
Effect of serum diamine oxidase activity derived from response to chemotherapy on adverse events and serum amino acid concentrations for esophageal cancer.
Authors: Sato Yuta , Tajima Jesse Yu , Tanaka Yoshihiro , Matsuhashi Nobuhisa 
Published: August 2024

55 Background: The relationship between activity of the small intestinal villi and the effectiveness of chemotherapy remains unclear. This study aimed to investigate how serum diamine oxidase (DAO) activity affects antitumor effects, adverse events, and amino acid absorption. Methods: We performed a single-center prospective cohort study that enrolled 50 patients with esophageal cancer (EC) receiving docetaxel, cisplatin, and 5-fluorouracil therapy. We determined the cut-off value of serum DAO activity contributing to a response to chemotherapy using a generalized additive model. Additionally, we compared adverse events, inflammatory markers, blood amino acid levels, and quality of life between the high and low DAO activity groups during chemotherapy. Results: The cut-off value of serum DAO activity at the first visit that contributed to a chemotherapy response was 6.5 units/L. Leukopenia and neutropenia of Grade ≥3 were significantly higher in the DAO low (<6.5 units/L) group ( p = 0.044, 0.017, respectively). Interleukin-6 was significantly lower in the DAO high (≥6.5 units/L) group at the first visit and at 4 weeks after the end of chemotherapy ( p = 0.039, 0.011, respectively). Glutamine was higher in the DAO high group at all measurement points during chemotherapy. Fatigue was significantly lower in the DAO high group ( p = 0.001). Conclusions: Serum DAO activity may be a predictor of the response to chemotherapy in patients with EC. The absorption capacity of amino acids was maintained in the group with high DAO activity, which may have contributed to the anti-inflammatory effect and provided a background for reducing adverse events. Clinical trial information: UMIN000048273 .
Correlation of enriched specific subset of immune cells nearby tumor associated macrophage (TAM) with pathologic complete response (pCR) of concurrent chemoradiotherapy followed by nivolumab in locally advanced rectal cancer (LARC).
Authors: Imai Mitsuho , Bando Hideaki , Tsukada Yuichiro , Inamori Koji , Kato Takeshi , Komatsu Yoshito , Uemura Mamoru , Yuki Satoshi , Taketomi Akinobu , Fujisawa Takao , Nakamura Yoshiaki , Kojima Motohiro , Koyama Shohei , Song Sanghoon , Ock Chan-Young , Nishikawa Hiroyoshi , Ito Masaaki , Yoshino Takayuki 
Published: August 2024

58 Background: We previously reported tumor-infiltrating lymphocyte (TIL) dynamics predictive of pCR in microsatellite-stable (MSS) LARC. In the current analysis, we investigate whether an immune cell-to-cell spatial network may predict pCR in MSS LARC. Methods: VOLTAGE study is a phase I/II study to evaluate the efficacy of chemoradiotherapy (CRT) followed by nivolumab and subsequent surgery in LARC pts. H&E images and multiplex immunofluorescence (mIF) images containing a total of 35 markers for T cells, TAM, Myeloid-derived suppressor cells, and Dendritic cells were analyzed with the Lunit SCOPE platform (Lunit, Republic of Korea). The proportion of T cells among all DAPI-positive (-pos) cells in a 50-micrometer radius centered on the TAM cells was counted. Results: In the samples of MSS LARC pts gathered at baseline, pre-treatment (n=38), TIL density in tumor microenvironment (TME) analyzed by H&E images was significantly correlated with the proportions of CD8-pos, CD4-pos, and FOXP3-pos cells (coefficient [coeff] 0.635, 0.482, and 0.580, respectively), but loosely correlated with PDL1-pos, PD1-pos, and CTLA4-pos cells (coeff 0.255, 0.174, and 0.180, respectively). Interestingly, intratumoral TIL density was more strongly correlated with TAM markers such as CD68 (coeff 0.269), compared to stromal TIL density (coeff 0.086). pCR rate was 28.9% in all MSS LARC, with baseline TIL density in TME predicting pCR with area under the receiver operating characteristic curve (AUROC) of 0.636 (p = 0.101). Interestingly, the ratio of baseline PDL1-pos cell proportion nearby CD68-pos cells, over that in all TME area (hereafter referred to as 'TAM-PDL1-proximity score') showed the best predictive performance for pCR, with an AUROC of 0.768 (p = 0.005). At the optimal cutoff of 1.66 times TAM-PDL1-proximity score, pCR rates for pts ≥ the cutoff and < the cutoff were 44% (11/25) and 0% (0/13), respectively (p = 0.006). Conclusions: PDL1-expressing immune cells nearby tumor associated macrophages before treatment is a promising predictive biomarker for pCR of neoadjuvant CRT followed by nivolumab in MSS LARC.