tbuckley/cabot-search huggingface dataset:
Prognosis and tumor-infiltrating lymphocytes (TILs) in estrogen receptor (ER)-low metastatic breast cancer (MBC): Analysis from a large multi-institutional cohort and the TONIC phase II trial with nivolumab.
Authors: Federica Miglietta, Claudio Vernieri, Manon de Graaf, Fabio Secomandi, Matilde Cacciatore, Andrea Botticelli, Andrea Vingiani, Giuseppe Fotia, Gaia Griguolo, Tommaso Giarratano, Valerio Pellegrini, Daniela Iannaccone, Francesca Porra, Matteo Fassan, Giancarlo Pruneri, Angelo Paolo Dei Tos, Valentina Guarneri, Marleen Kok, Maria Vittoria Dieci
Journal: Journal of Clinical Oncology (2024)

1100 Background: Although 1% as ER cutoff to discriminate ER+/HER2- from triple-negative (TN) BC serves the purpose of maximizing access to endocrine therapy, it may be suboptimally informative in terms of prognosis and immune checkpoint inhibitor (ICI) benefit. In the early setting, we reported that ER-low BC (ER 1-9%/HER2-) is immunologically and prognostically similar to TN (ER 0%) [Massa, 2023]. Here we focus on MBC and aim to assess prognosis of ER-low BC, including the conversion from ER+(≥10%)/HER2- to ER-low at relapse. We also compared ER-low and TN in terms of outcome after ICI, and TILs. Methods: We included two cohorts of MBC patients (pts): a multicentric retrospective cohort and pts with ER&lt;10%/HER2- MBC enrolled in the TONIC trial testing nivolumab +/- induction therapy. All pts had ER and HER2 status assessed on metastatic tumor lesion; in the retrospective cohort ER and HER2 status on primary tumor was also available. Survival endpoints in the retrospective cohort: overall survival (OS, from BC diagnosis), post-relapse survival (PRS, from BC relapse). Exploratory endpoints from the TONIC trial: clinical benefit rate (CBR), OS and PFS (both from randomization). TILs were assessed on MBC samples (both cohorts) and on matched primary tumor (retrospective cohort). Results: We included 1112 pts in the retrospective cohort: the prevalence of ER-low BC was 3.6% in primary tumor and 5.9% in MBC lesions. In the TONIC trial, 15/110 pts had ER-low MBC. In the retrospective cohort, ER-low and TN MBC showed similar outcome, and significantly unfavorable vs ER+/HER2- MBC (Table). Among pts with ER+/HER2- primary BC, 6.7% converted to ER-low and 14.7% to TN at relapse. ER+/HER2- BC pts converting to ER-low had similar outcome than those converted to TN, and significantly poorer than pts with stable ER+/HER2- (Table). In the TONIC trial, ER-low MBC pts, compared to TN, showed similar response to ICI (CBR: 20.0% vs 22.1%, p=1), similar PFS and numerically worse OS (Table). TIL levels on MBC samples were similar between ER-low and TN both in the retrospective (median: 6% vs 5%, p=0.83) and the TONIC cohorts (median: 5.5% vs 5.0%, p=0.56) and were higher than ER+/HER2- (median: 3%). Conclusions: We confirmed that ER-low and TN MBC show similar poor outcome and the shift from ER+/HER2- to ER-low has a comparable unfavorable prognostic impact compared to conversion to TN. Our results support the hypothesis that ER-low and TN are immunologically akin and similarly prone to respond to ICI. [Table: see text]
Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study
Authors: Akihito Kawazoe, Rui-Hua Xu, Pilar García-Alfonso, Maria Passhak, Hao-Wei Teng, Ardaman Shergill, Mahmut Gumus, Camilla Qvortrup, Sebastian Stintzing, Kathryn Towns, Tae Won Kim, Kai Keen Shiu, Juan Cundom, Sumitra Ananda, Andrey Lebedinets, Rong Fu, Rishi Jain, David Adelberg, Volker Heinemann, Takayuki Yoshino, Elena Elez, Juan Cundom, Ezequiel Slutsky, Julieta Grasselli, Luis Fein, Luciana Bella Quero, Warren Joubert, Peter Gibbs, Timothy Price, Matthew Burge, Sumitra Ananda, Muhammad Khattak, Bruce Colwell, Felix Couture, Brandon Meyers, Kathryn Towns, Michael Sawyer, Lucas Sideris, Ruihua Xu, Wei Wang, Hongming Pan, Per Pfeiffer, Lars Henrik Jensen, Camilla Qvortrup, Sebastian Stintzing, Dirk Arnold, Sylvie Lorenzen, Stefan Kubicka, Reinhard Depenbusch, Maria Passhak, Ravit Geva, Ayala Hubert, Einat Shacham-Shmueli, Gleb Kornev, Akihito Kawazoe, Toshiki Masuishi, Atsuo Takashima, Hiroki Hara, Hisato Kawakami, Nozomu Machida, Kentaro Yamazaki, Hisateru Yasui, Akihito Tsuji, Taito Esaki, Kensei Yamaguchi, Tae-You Kim, Joong Bae Ahn, Myung Ah Lee, Tae Won Kim, Joon Oh Park, Soohyeon Lee, Rashida Orlova, Vladislav Sarzhevskiy, Marina Sekacheva, Sergey Tjulandin, Oksana Shirokova, Alsu Iskhakova, Andrey Lebedinets, Paula Jimenez Fonseca, Fernando Rivera Herrero, Elena Elez Fernandez, Pilar Garcia Alfonso, Maria Jose Gomez Reina, Kun-Huei Yeh, Hao-Wei Teng, Tsai Sheng Yang, Hwei-Ming Wang, Yu-Min Yeh, Mustafa Ozguroglu, Mahmut Gumus, Suayib Yalcin, Bulent Erdogan, Umut Demirci, Pinar Gursoy, Hakan Harputluoglu, Atakan Demir, Kai-Keen Shiu, Ewan Brown, Paul Ross, Elizabeth Smyth, Ian Chau, Mark Saunders, Gina Vaccaro, Steven McCune, Raymond Wadlow, Gazala Khan, Babar Bashir, Michael Koontz, Ludmila Martin, Ardaman Shergill, Patrick Cobb, Mark Kochenderfer
Journal: Journal of Clinical Oncology (2024)

Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC.
Effect of a learning-based approach using the echo-signals obtained by a single-unit transducer on detection of breast tumors.
Authors: Hyeong-Gon Moon, Jinyoung Byeon, Yunna Lee, Jong-Ho Cheun, Young-Gon Kim, Kyoung Min Kim
Journal: Journal of Clinical Oncology (2024)

1566 Background: Breast cancer mortalities in the less developed countries are predicted to increase over the next decades mainly due to the low utilization rates of breast cancer screening programs. Additionally, studies have shown that the sensitivity and accuracy of breast self-examination in women are suboptimal. Therefore, it is important to develop a novel and affordable technology that can accurately detect small breast tumors in women. We have developed a deep learning-based echo- signal processing system that can detect breast tumors with high sensitivity and accuracy by merely obtaining ego-motion estimated echo-signals generated by a single-unit piezoelectric transducer system. Methods: We have prospectively collected echo-signals using a single-unit piezoelectric transducer system in 200 patients with breast tumors who underwent curative surgery at the Seoul National University Hospital and SMG-SNU Boramae Medical Center between Oct 2022 and Feb 2024. The data from the first 131 cases was used for the training and testing of the deep learning model with the ratio of 8:2, and the subsequent data from 69 cases was used for the external validation. We used ImageNet pre-trained ResNet50 model to train the deep learning model and adopted various data augmentation methods for model robustness. Five nested cross-validation was used to ensure the generalization performance. Results: The median age of the enrolled patients was 55 (IOR, 47-63) and 65 patients (32.5%) had non-palpable breast tumors. Nearly half of the patients (n=93, 46.5%) had tumors smaller than 2.0 cm in the largest dimension. Our deep learning algorithm showed outstanding performance with the area under the curve (AUC) of 0.914±0.022 and 0.964±0.011 for the image- and region-level, respectively, in the training and testing set (n=131). In the external validation set (n=69), the model demonstrated an AUC of 0.846±0.012 and 0.932±0.009 for the image- and region-level, respectively. As shown (Table), the accuracy, sensitivity, and specificity were substantially improved for the region-level analysis when compared with those of the image-level analysis. Conclusions: Using a prospectively collected data from 200 patients, we developed a highly accurate and robust deep learning model to detect breast tumors in women by processing echo-signals obtained by a single-unit piezoelectric transducer system. Our data indicate that deep learning approach based on low-volume echo signal can lead to a novel and affordable breast tumor screening strategy that can improve early breast cancer detection.[Table: see text]
Safety and efficacy of interleukin-6 blockade for immune-related adverse events: A systematic review and meta-analysis.
Authors: Maysa Vilbert, Erica C. Koch Hein, Thiago Madeira, Isabella Michelon, Jonathan N. Priantti, Matheus Lobo, Maria Inez Dacoregio, Caio Castro, Ludimila Cavalcante, Chia-Yun Wu, Sherin Juliet Rouhani, Ross D Merkin, Ryan J. Sullivan, Kerry Lynn Reynolds
Journal: Journal of Clinical Oncology (2024)

e24149 Background: Interleukin-6 blockade (IL-6) - tocilizumab and sarilumab - have shown promising results for steroid-refractory immune-related adverse events (irAEs) in cancer patients treated with immune-checkpoint inhibitors (ICI). However, the ideal scenario for IL-6 therapy use is not well established. Hence, we conducted a systematic review and meta-analysis to investigate the safety and efficacy of IL-6 blockade for patients with ICI-associated irAEs. Methods: PubMed, Embase, and Cochrane databases were searched for studies including at least five patients with ICI-associated irAEs treated with IL-6 blockade. The main outcomes were safety and efficacy, measured as clinical improvement (resolution or improvement of irAEs or steroid taper to &lt; 10mg daily), C-reactive protein (CRP) level changes, and elevated IL-6 levels. Analyses using random-effects model were done in R Software. Heterogeneity was assessed using I 2 . Results: Eight studies with 202 patients were included: 1 clinical trial, 3 multicenter, and 4 single-center observational studies. The median age was 63 years (30-81), and 59% were male. Melanoma was the predominant tumor type (n = 78, 38.6%), followed by lung (n = 67, 33%), renal cell carcinoma (n = 21, 10%), bladder cancer (n = 12, 6%), and others. Monotherapy with ICI, targeting PD-1, PD-L1, or CTLA-4, was given to 77% of patients, while 23% had combination ICI therapy. Follow-up ranged from 6 to 23 months. Most patients received prior steroids (85%) or steroid-sparing immunosuppression (24%). Pooled analysis of all patients showed an overall clinical improvement rate of 87.9% (95%CI 78.7 to 95.1, I 2 = 44%). Clinical improvement with IL-6 blockade was significantly higher in patients with cytokine release syndrome (CRS, 100%) and rheumatic irAEs (88%) compared to other irAEs (p &lt; 0.01, Table 1). At the time of irAEs, the median CRP level was 109.3 (11.5 to 233), which decreased to 17 (1 to 60) after IL-6 blockade. The frequency of baseline elevated IL-6 level was 90.6% (95%CI 68 to 100, I 2 = 80%). Grade 3 or 4 IL-6-related adverse events were reported in 11% (17/151) of patients and included neutropenia (n = 6), increased liver transaminase levels (n = 4), and gastrointestinal perforation (n = 2). Conclusions: This systematic review and meta-analysis provides evidence for the use of IL-6 blockade for steroid-treating refractory irAEs associated with ICI. The vast majority of patients with steroid-refractory CRS and rheumatic irAEs were successfully treated with anti-IL6 therapy.[Table: see text]
Alleviating lung injury and pulmonary fibrosis in radiotherapy-immunotherapy combination: The role of low-dose radiation therapy.
Authors: Yu Wang, Shengfa Su
Journal: Journal of Clinical Oncology (2024)

e14632 Background: Lung cancer continues to be the primary cause of cancer-related mortality on a global scale. The integration of radiotherapy and immunotherapy has yielded significant advancements in the treatment of locally advanced non-small cell lung cancer. However, the occurrence of treatment-associated pneumonia remains the predominant adverse event necessitating treatment cessation and permanent medication discontinuation. The immune-modulating effects of radiation therapy on the body contribute to a complex interplay between radiation and inflammation. Low-dose radiotherapy (LD-RT) has historically been utilized for the management of benign inflammatory conditions. Recently, LD-RT was found to be effective in treating severe pneumonia in patients with severe COVID-19 as well as acute respiratory distress syndrome (ARDS). This investigation seeks to examine the impact of LD-RT on lung tissue morphology and the inflammatory immune microenvironment in preclinical models of lung injury induced by high-dose radiotherapy combined with programmed death-1(PD-1) inhibitor therapy. Methods: 6-8 week old C57BL/6 mice were treated with a single high-dose thoracic radiotherapy (15Gy) and the PD-1 inhibitor (once a week), with or without the low-dose radiotherapy (1.0/1.5Gy) four weeks later. Lung tissue was collected one and a half months and three months respectively after the initial high-dose radiotherapy for evaluation using HE and Masson staining, Image J software for analysis of collagen volume fraction (CVF), and immunohistochemical staining for CD3+ and CD8+ T lymphocytes. Cytokine transforming growth factor (TGF)-β1、interleukin (IL)-6 and tumor necrosis factor (TNF)-α level in lung tissue was detected by ELISA. Statistical analysis was performed using GraphPad Prism 9.5.0 software. Results: The radiotherapy-immunotherapy combination (iRT) group exhibits notable lung injury characterized by the proliferation of alveolar type II epithelial cells, thickening of alveolar septa, interstitial edema, pulmonary congestion and bleeding, increased infiltration of inflammatory cells, and significant deposition of interstitial collagen fibers. In contrast, the iRT+ LD-RT group demonstrates a significant decrease in lung tissue damage, interstitial fibrosis, collagen volume fraction (CVF), levels of IL-6 and TGF-β, as well as the infiltration of CD3+ and CD8+T cells compared to the iRT group. Conclusions: Low-dose radiation has the potential to ameliorate lung injury induced by the combination of radiotherapy and PD-1 inhibitors by modulating the inflammatory milieu, thereby potentially mitigating the development of pulmonary fibrosis.
Can patients with biopsy-diagnosed DCIS safely spare sentinel lymph node biopsy (SLNB)?
Authors: Xinyu Li, Yudong Li, Qiang Liu
Journal: Journal of Clinical Oncology (2024)

e12583 Background: While the guidelines generally recommend that most patients with biopsy-diagnosed breast ductal carcinoma in situ (DCIS) can be spared from axillary staging if receiving breast conserving surgery, the percentage of such patients received SLNB is still as high as 50-70%. SOUND trial recently provides some low risk invasive breast cancer patients with the option of omitting SLNB, further highlighting the necessity of omitting SLNB in DCIS patients. This study aimed to retrospectively analyze the chance of turning into invasive cancer and lymph node metastasis in the patients who are diagnosed as DCIS by biopsy. Methods: Preoperative biopsy-diagnosed breast pure DCIS patients between 2011-2023 were retrospectively reviewed in Sun Yat-sen Memorial Hospital. Patients with axilla staging were grouped by pathology status (LN- versus LN+). Differences were compared using either t test or chi-squared test. Multi-variate logistic regression model was conducted to stratify the risk for LN metastasis. Results: 1193 patients were eligible for analysis, of whom 51.8% turned invasive breast cancer (IBC) in post-surgery pathology. 42% and 81% of IBCs were only T1 mi and less than 1cm foci (T1a,b) respectively. 1161 (97.3%) patients had available axilla LN information and their axillary metastasis rate was 7.1% (0.9% and 12.5% in DCIS and IBC). Only 22 (1.9%) or 15 (1.3%) patients had ≥ 3 or 4 positive LN involved. Multi-variate analysis identified four risk factors associated with LN metastasis: ultrasound suspicious lymph node (OR=2.22, 95%CI: 1.21-4.07), tumor size (&gt;2cm vs ≤2cm: OR=2.85, 95%CI:1.10-7.42), biopsy method (core biopsy vs excision: OR=7.04, 95%CI:1.60-31.25) and necrosis (OR=2.20, 95%CI: 1.23-3.94). Among 440 patients with excision biopsy, only 1.4% had LN involved. In the other 721 patients diagnosed by core biopsy, the LN metastasis rate of patients who had 0,1,2 and 3 risk factors were 3.6%, 6%, 21% and 29.5%, respectively. Based on the number of risk factors patients were stratified to low risk (having 0-1 risk factor) and high risk (having ≥2 risk factors), with low risk patients having only 5.4% LN metastasis. Conclusions: Although the patients diagnosed with preoperative pure DCIS had a high chance of upgrading to invasive cancer, only 7.1% of them had lymph node metastasis. 98% of them are Z0011-eligible and 40% of them are SOUND-eligible if they receive breast conserving surgery, indicating the futility of axillary staging in these patients. We identified four independent risk factors for LN metastasis (suspicious lymph node on US, tumor size, biopsy method and necrosis). Even in the patients who received mastectomy, if they have only 0-1 risk factors, SLNB can still be safely omitted.
Letter to the editor for the article“efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study”
Authors: Lexin Wang, Qibiao Wu, Hao Chi, Guanhu Yang
Journal: International Journal of Surgery (2024)

aFaculty of Chinese Medicine, and State Key Laboratory of Quality Research in Chinese Medicine, and University Hospital, Macau University of Science and Technology, Macau, Macao SAR, China bGeneral Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China cNingxia Medical University, Yinchuan, Ningxia 750000, China dClinical Medical College, Southwest Medical University, Luzhou 646000, China eDepartment of Specialty Medicine, Ohio University, Athens 45701, OH, United States Lexin Wang, Qibiao Wu and Hao Chi: These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Faculty of Chinese Medicine, and State Key Laboratory of Quality Research in Chinese Medicine, and University Hospital, Macau University of Science and Technology, Macau, Macao SAR, China, Department of Specialty Medicine, Ohio University, Athens 45701, OH, United States. E-mail address: [email protected] (G. Yang) This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Cardiomyopathy among recipients of immune checkpoint inhibitor therapy: A prospective study.
Authors: Haoyi Zheng, Matthew J. Granville, Genie Miraglia, Emily Okin, Jonathan Weber, Stephanie Solito, Sherly Jacob-Perez, Su Yun Chung, Rajasree Roy, Christina Trotta, Dilip Patel, Richard Shlofmitz, Jane Cao, Omar K. Khalique, Ziad Ali, Roosha Parikh, Rita Jermyn, Elizabeth Haag, Bhoomi Mehrotra, Syed S. Mahmood
Journal: Journal of Clinical Oncology (2024)

e24025 Background: Patients treated with immune checkpoint inhibitors (ICI) may develop cardiomyopathy, but data are limited on the rate of cardiomyopathy incidence. The aim of this study was to assess the occurrence of cardiomyopathy among ICI recipients. Methods: In this prospective surveillance study, echocardiograms and EKG were performed at baseline, and quarterly during the first year of ICI therapy. New or worsening cardiomyopathy was defined as left ventricular ejection fraction (EF) decline of &gt; 10% from baseline to &lt; 50%. B-type natriuretic peptide (BNP) and troponin were assessed weekly during the first three weeks of ICI therapy. Subsequent troponin for myocarditis assessment was tested as needed per treating oncology team. Results: A total of 23 patients were enrolled with mean age 73±10 years, 35% female, 74% Caucasian, and body mass index 31±7 kg/m2. Cardiovascular risk factors included hypertension (86%), diabetes mellitus (29%), myocardial infarction (19%) and smoking (10%), and prior radiation treatment (30%). Malignancies included lung cancer (50%), renal cell carcinoma (14%), and Merkel cell carcinoma or urothelial carcinoma (9% each). ICI regimen included pembrolizumab (48%), nivolumab (43%), and ipilimumab or atezolizumab (4% each). There was no change in weekly troponin or BNP, or quarterly QRS duration on EKG, and no myocarditis cases were observed. Between baseline and at 1-year since ICI therapy initiation, there was no change in QRS duration on EKG, as well as no change in median LVEF (59% [IQR 46-67] vs 61% [IQR 58-65], p = 0.48), or global longitudinal strain (18% [IQR 15-20]) vs 19% [IQR 18-21], p = 0.11). New cardiomyopathy occurred in 1 (4%) patient at 3 months following ICI initiation with LVEF drop from 53% to 38% and without troponin elevation to suggest myocarditis, corresponding to an incidence rate of 43.5 cases per 1000 person-years of observation. Conclusions: In this prospective surveillance study, new cardiomyopathy was observed after ICI treatment, although the incidence was low. Larger studies are needed to confirm these findings.