tbuckley/cabot-search huggingface dataset:
Comparative analysis of mortality and hospital expenditure in patients with gastroenterological cancer: Thailand and United States.
Authors: Thanathip Suenghataiphorn, Wasin Laohavinij, Tuntanut Lohawatcharagul
Journal: Journal of Clinical Oncology (2024)

79 Background: Concerns about rising health care cost and quality of care has been a major health issue worldwide. Gastrointestinal (GI) cancer accounts for one-quarter of the global cancer incidence. However, there are limited evidence, which demonstrates the differences in clinical outcome and economic burden of GI cancer when comparing between health care setting of developed and developing countries. Methods: Two data sources were analyzed: (i) The 2020 U.S. National Inpatient Sample (NIS) involving patients that were primarily discharged with gastroenterological cancer, and (ii) data at tertiary care center in Thailand used for this comparative study, with similar period and conditions. Participants were identified using relevant ICD-10 CM codes. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariate logistic and linear regression analyses. Participants are divided into those who experienced mortality and those who survived. We report crude mortality rates and expenditure outcomes. Statistical significance was established at a p-value of 0.05. Results: We identified 9,299 Thai records and estimated 216,859 US records with a primary diagnosis of GI cancer at discharge. Of these, 2.15% (200/9,299) of the Thai records and 3.82% (8,285/216,859) of the US records died. In a multivariate analysis, death during hospitalization is associated with higher length of stay (Thai: b = 18.10, 95% CI (16.71, 19.49), p &lt; 0.001), (US: b = 3.38, 95% CI 3.38 (2.14, 4.63), p &lt; 0.001) and higher hospitalization charges (Thai: b = 155,530.02 THB, 95% CI (141,805.10, 169,254.80), p &lt; 0.001), (US: b = 46,882.44 USD, 95% CI (31,629.51, 62,135.37), p &lt;0.001). Subpopulation analysis revealed similar significant results. We observed higher increased length of stay in Thailand, whereas higher crude mortality rate and hospitalization charges was observed in the United States. Conclusions: In both Thailand and United States, mortality in patient with GI cancer is associated with increase in length of stay and higher hospitalization expenses. However, the magnitude of difference in each outcome differs between two countries. Future studies investigating health care costs, cultural role and clinical outcomes may provide insights for cost-reduction strategies, while maintaining or improving the current standard of care in this population group. [Table: see text]
Pretreatment CT-based machine learning radiomics model to predict response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy.
Authors: Changzhen Shang, Yonglin Hua, Yajin Chen, Hongkai Zhuang
Journal: Journal of Clinical Oncology (2024)

94 Background: Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy has demonstrated promising treatment effects in unresectable hepatocellular carcinoma (uHCC). However, biomarkers for predicting the response to LPI therapy remained to be further explored. The current study aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy for uHCC. Methods: Clinical data of patients who were diagnosed with uHCC and accepted LPI therapy were collected in our institution. The clinical model was built by clinicopathological information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was utilized as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores. Results: 151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three patients achieved complete response, 69 showed partial response, 46 showed stable disease and 33 showed progressive disease (evaluated by mRECIST criteria). The objective response rate (ORR), disease control rate (DCR), and conversion resection rate were 47.7, 78.1 and 23.2%, respectively. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model could categorize participants into high- and low-risk groups for progression-free survival and overall survival in the training and validation sets. Conclusions: The current study developed a novel and promising machine learning radiomics model, which could efficiently predict the efficacy of LPI therapy for uHCC, with comparable performance to clinical-radiomics model.
Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).
Authors: Hongru Li, Xiao jie Yang, Tianxing Guo, Jiabin Fang, Nengluan Xu, Sufang Chen, Qiongyao Zhang, Ying Lin, Xiaojie Pan
Journal: Journal of Clinical Oncology (2024)

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.
Examining molecular landscape and drug sensitivity profiles of patient-derived xenografts from resected brain metastases.
Authors: Aki Morikawa, Tusharika Rastogi, Peter Ulintz, Habib Serhan, Edwin Nieblas-Bedolla, Jason Heth, Xu Cheng, Liwei Bao, Aaron M. Udager, Matthew Soellner, Nathan Merrill, Sofia Diana Merajver
Journal: Journal of Clinical Oncology (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.
Beyond discrete-choice options
Authors: Amir Hosein Hadian Rasanan, Nathan J. Evans, Laura Fontanesi, Catherine Manning, Cynthia Huang-Pollock, Dora Matzke, Andrew Heathcote, Jörg Rieskamp, Maarten Speekenbrink, Michael J. Frank, Stefano Palminteri, Christopher G. Lucas, Jerome R. Busemeyer, Roger Ratcliff, Jamal Amani Rad
Journal: Trends in Cognitive Sciences (2024)

While decision theories have evolved over the past five decades, their focus has largely been on choices among a limited number of discrete options, even though many real-world situations have a continuous-option space. Recently, theories have attempted to address decisions with continuous-option spaces, and several computational models have been proposed within the sequential sampling framework to explain how we make a decision in continuous-option space. This article aims to review the main attempts to understand decisions on continuous-option spaces, give an overview of applications of these types of decisions, and present puzzles to be addressed by future developments.
Efficacy and safety analysis on the combination of camrelizumab with nab-paclitaxel and cisplatin-based chemotherapy in first-line treatment of advanced or metastatic esophageal squamous cell carcinoma.
Authors: Xiaofeng Cong, Zijun Xu, Ziling Liu
Journal: Journal of Clinical Oncology (2024)

205 Background: Nab-paclitaxel has indicated good efficacy during the multi-line esophageal squamous cell carcinoma (ESCC) treatment. Our study summarized the efficacy and safety of the first-line combination treatment of camrelizumab with nab-paclitaxel and platinum in advanced or metastatic ESCC patients. This could provide evidence of the positive effects of using nab-paclitaxel. Methods: We included patients with advanced or metastatic ESCC who received camrelizumab in association with nab-paclitaxel and cisplatin for 3-6 cycles as first-line therapy. The patients were recruited from the First Hospital of Jilin University between August 2021 and December 2023. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), PFS, and OS rates at 12, 18, and 24 months, including safety. Results: 43 patients were included in this study, they were assessed based on the therapeutic effect, with 72.1% [95% CI,58.1%-86.1%]ORR and 100% DCR. The median PFS was 25.5 months, and the median OS was not achieved. The OS rates were 96.8%, 86.4%, and 78.6% at 12 months, 18 months, and 24 months, respectively. In contrast, the PFS rates were 90.1%, 75.8%, and 68.3%, respectively. Grade 3 or above treatment-related adverse reactions (TRAEs) occurred in nine patients (20.9%). No patient developed severe grade 5 TRAEs. Conclusions: During the first-line treatment of advanced or metastatic ESCC, applying nab-paclitaxel in associated with camrelizumab and cisplatin -based therapy showed a positive effect. Therefore, the results exhibit an extension of OS and PFS with manageable safety and no new TRAEs.
Validation of a chemotherapy toxicity prediction model in older adults with cancer in Taiwan.
Authors: Chieh-Ying Chang, Yu-Shin Hung, Ming-Chung Kuo, Chih-Chung Hsu, Jen-Shi Chen, Wen-Chi Chou
Journal: Journal of Clinical Oncology (2024)

223 Background: The Cancer and Aging Research Group (CARG) model is established for predicting chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese or non-solid tumor populations. Due to biopsychosocial distinctions in the Taiwanese demographic and inherent disparities between lymphoma and solid tumors, a modified CARG (mCARG) was assessed for its toxicity prediction capabilities. Methods: In this study, 337 consecutive patients aged ≥65 years with solid tumors (N=258) or lymphoma (N=79), slated for first-line chemotherapy, were recruited from a single medical center in Taiwan between 2018 and 2021, with follow-up until December 31, 2021. Patients were categorized into low-, medium-, and high-risk groups based on mCARG, excluding the cancer-type parameter from the original CARG variables. Validation of mCARG involved receiver operating characteristic (ROC) curves, and individual mCARG variables were analyzed using univariate analysis for their impact on chemotherapy toxicities and overall survival. Results: This study included 337 patients (mean age, 70 years; 160 female [47%]; 177 male [53%]) classified as low-(N=112, 33.2%), medium-(N=106, 31.5%), and high-(N=119, 35.3%) risk. Toxicities of grades ≥3 were 41.1%, 50.0%, and 71.4% ( P&lt;0.001), respectively. ROC was 0.665 (95% CI: 0.608–0.722), indicating satisfactory discrimination. However, the lymphoma subgroup exhibited no significant differences in toxicity risk levels (70.0%, 74.1%, and 81.0%; P=0.39). Among mCARG variables, age ≥72 years ( P=0.008), polychemotherapy ( P=0.009), decreased hemoglobin ( P&lt;0.001), falls ( P=0.008), and inability to walk one block ( P=0.01) were associated with toxicities. One-year overall survival rates were 80.6%, 69.4%, and 57.2%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival ( P=0.001). Conclusions: This prognostic study validated the mCARG model in a heterogeneous cancer cohort in Taiwan but failed to do so in the lymphoma subgroup. Although unable to predict all toxicities, mCARG could offer insights into patient survival among older individuals with cancer.
Association between the occurrence of immune-related adverse events and survival outcomes in patients with cancer treated with perioperative immune checkpoint inhibitors: A systematic review and meta-analysis.
Authors: Taiga Komatsu, Kohei Chida, Nobuyuki Horita, Alessio Cortellini, Abdul Rafeh Naqash, Yu Fujiwara
Journal: Journal of Clinical Oncology (2024)

39 Background: Although multiple studies have revealed that the occurrence of immune-related adverse events (irAEs) is associated with better survival in patients with advanced cancer, the association in patients with early-stage disease in the perioperative setting remains unclear. We performed a systematic review and meta-analysis to evaluate this association in the neoadjuvant and adjuvant settings. Methods: We performed a database search in PubMed/MEDLINE and Embase to identify eligible articles up to March 2024. We included studies evaluating the association between the occurrence of irAEs and survival outcomes in patients with solid tumors receiving at least one ICI in the perioperative setting. Cancer type, ICI agent, the number of patients, and survival outcomes (hazard ratio [HR] with 95% confidence interval [CI]) were summarized. We performed a random-effect model meta-analysis of survival outcomes that contained HR and 95% CI information from more than two studies. Results: After screening 884 articles, we found 15 eligible articles of which four studies reporting only treatment-related adverse events without irAE information were excluded. Finally, 11 studies (Clinical trials: n=3, Cohort studies: n=8) analyzing the association between the incidence of irAEs and survival were identified. Melanoma, triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and urothelial carcinoma were evaluated in seven, two, one, and one study, respectively. While ten studies defined the irAE group as any-type and any-grade irAEs, one study defined the irAE group as any-type and grade 2-5 irAEs. OS was evaluated in five studies (four studies for melanoma), of which two studies suggested that the occurrence of irAEs was associated with longer OS. A meta-analysis of three studies showed a tendency of the association between the occurrence of any-type and any-grade irAEs and longer OS (Pooled HR=0.69, 95% CI 0.47-1.00, p = 0.05). RFS was evaluated in eight studies (seven for melanoma), of which seven studies indicated the association between the incidence of any-type irAEs (any-grade: 6 studies, grade 2-5: 1 study) and longer RFS. A meta-analysis of five studies revealed a significant association between the occurrence of any-type irAEs (any-grade: 4 studies, grade 2-5: 1 study) and longer RFS (Pooled HR=0.52, 95% CI 0.41 - 0.67, p &lt; 0.0001]); however, Funnel plot indicated a presence of publication bias. Conclusions: This study suggests an association between irAEs and longer survival from perioperative ICI therapy, particularly in patients with melanoma. The result should be cautiously interpreted given a possible presence of publication and immortal bias. Further prospective studies and individual patient data meta-analysis are needed to validate this result.
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: Mitsuho Imai, Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Takeshi Kato, Yoshito Komatsu, Mamoru Uemura, Satoshi Yuki, Akinobu Taketomi, Takao Fujisawa, Yoshiaki Nakamura, Motohiro Kojima, Shohei Koyama, Sanghoon Song, Chan-Young Ock, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (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&amp;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&amp;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 &lt; 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.