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Cai M, Song B, He D, Xu C, Luo R, Qian Y, Kam S, Huo X, Wang J, Vieth M, Zhong Y. Endoscopic resection after downstaging of oesophageal carcinoma by neoadjuvant chemoimmunotherapy: - a new multimodal concept? Gut 2025:gutjnl-2024-333337. [PMID: 40139748 DOI: 10.1136/gutjnl-2024-333337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 01/23/2025] [Indexed: 03/29/2025]
Affiliation(s)
- Mingyan Cai
- Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Baohui Song
- Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Dongli He
- Zhongshan Hospital Xuhui Branch, Fudan University, Shanghai, China
| | - Chen Xu
- Pathology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Rongkui Luo
- Pathology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Yang Qian
- Department of Radiation Oncology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Sikei Kam
- Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Xucheng Huo
- Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Jian Wang
- Department of Radiotherapy, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Yunshi Zhong
- Zhongshan Hospital Fudan University, Shanghai, Shanghai, China
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Rusu-Both R, Socaci MC, Palagos AI, Buzoianu C, Avram C, Vălean H, Chira RI. A Deep Learning-Based Detection and Segmentation System for Multimodal Ultrasound Images in the Evaluation of Superficial Lymph Node Metastases. J Clin Med 2025; 14:1828. [PMID: 40142635 PMCID: PMC11942978 DOI: 10.3390/jcm14061828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Even with today's advancements, cancer still represents a major cause of mortality worldwide. One important aspect of cancer progression that has a big impact on diagnosis, prognosis, and treatment plans is accurate lymph node metastasis evaluation. However, regardless of the imaging method used, this process is challenging and time-consuming. This research aimed to develop and validate an automatic detection and segmentation system for superficial lymph node evaluation based on multimodal ultrasound images, such as traditional B-mode, Doppler, and elastography, using deep learning techniques. Methods: The suggested approach incorporated a Mask R-CNN architecture designed specifically for the detection and segmentation of lymph nodes. The pipeline first involved noise reduction preprocessing, after which morphological and textural feature segmentation and analysis were performed. Vascularity and stiffness parameters were further examined in Doppler and elastography pictures. Metrics, including accuracy, mean average precision (mAP), and dice coefficient, were used to assess the system's performance during training and validation on a carefully selected dataset of annotated ultrasound pictures. Results: During testing, the Mask R-CNN model showed an accuracy of 92.56%, a COCO AP score of 60.7 and a validation score of 64. Furter on, to improve diagnostic capabilities, Doppler and elastography data were added. This allowed for improved performance across several types of ultrasound images and provided thorough insights into the morphology, vascularity, and stiffness of lymph nodes. Conclusions: This paper offers a novel use of deep learning for automated lymph node assessment in ultrasound imaging. This system offers a dependable tool for doctors to evaluate lymph node metastases efficiently by fusing sophisticated segmentation techniques with multimodal image processing. It has the potential to greatly enhance patient outcomes and diagnostic accuracy.
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Affiliation(s)
- Roxana Rusu-Both
- Automation Department, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (A.-I.P.); (C.B.); (H.V.)
| | | | - Adrian-Ionuț Palagos
- Automation Department, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (A.-I.P.); (C.B.); (H.V.)
- AIMed Soft Solution S.R.L., 400505 Cluj-Napoca, Romania;
| | - Corina Buzoianu
- Automation Department, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (A.-I.P.); (C.B.); (H.V.)
| | - Camelia Avram
- Automation Department, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (A.-I.P.); (C.B.); (H.V.)
| | - Honoriu Vălean
- Automation Department, Technical University of Cluj-Napoca, 400114 Cluj-Napoca, Romania; (A.-I.P.); (C.B.); (H.V.)
| | - Romeo-Ioan Chira
- Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania;
- Gastroenterology Department, Emergency Clinical County Hospital Cluj-Napoca, 400347 Cluj-Napoca, Romania
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Ahn Y, Choe J, Lee HJ, Park SR, Kim JH, Song HJ, Kim MJ, Kim YH. Diagnosing Complete Response to Preoperative Chemoradiation in Esophageal Cancer Using Dynamic Contrast-Enhanced MRI Response Criteria. Korean J Radiol 2025; 26:269-280. [PMID: 39999967 PMCID: PMC11865900 DOI: 10.3348/kjr.2024.0896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 12/18/2024] [Accepted: 12/19/2024] [Indexed: 02/27/2025] Open
Abstract
OBJECTIVE To assess the performance of novel qualitative diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to identify the pathologic complete response (pCR) of primary tumors in esophageal cancer after neoadjuvant chemoradiation (nCRT). MATERIALS AND METHODS Patients who underwent nCRT, subsequent MRI, positron emission tomography/computed tomography (PET/CT), endoscopy, or esophagectomy for esophageal cancer between October 2021 and October 2023 were retrospectively analyzed. The DCE-MRI response of primary tumors was interpreted using five grades by thoracic radiologists as follows: G1 (compatible with CR), G2 (probable CR), G3 (probable partial response [PR]), G4 (compatible with PR), and G5 (stable or progressive disease). The performances of MRI, PET/CT, endoscopy, and their combinations in diagnosing pCR in primary tumors were calculated. RESULTS A total of 52 patients (male:female, 46:6; age, 61.2 ± 8.0 years) were included. Surgical specimens revealed pCR (ypT0) in 34 patients. G1 as the MRI criterion for pCR of primary tumors yielded a positive predictive value (PPV), specificity of 100% (18/18), and low sensitivity (23.5% [8/34]). Combining G1 and G2 as the MRI criteria increased the sensitivity to 73.5% (25/34), with a specificity of 88.9% (16/18), accuracy of 78.8% (41/52), and PPV of 92.6% (25/27). Adding the DCE-MRI results (G1-2) significantly improved accuracy for both PET/CT (from 65.4% [34/52] to 80.8% [42/52], P = 0.03) and endoscopy (from 55.8% [29/52] to 76.9% [40/52], P = 0.005), with increase in sensitivity (from 55.9% [19/34] to 82.4% [28/34] for PET/CT-based evaluation [P = 0.008] and from 47.1% [16/34] to 82.4% [28/34] for endoscopy-based evaluation [P = 0.001]). CONCLUSION DCE-MRI-based grading shows high diagnostic performance for identifying pCR in primary tumors, particularly in terms of PPV and specificity, and enhances response evaluation when combined with PET/CT and endoscopy.
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Affiliation(s)
- Yura Ahn
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jooae Choe
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Hyun Joo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sook Ryun Park
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jong-Hoon Kim
- Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ho June Song
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistic, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Yong-Hee Kim
- Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
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Zhang G, Wu J, Ji M, Liu X, Shi M. SLC25A1 promotes lymph node metastasis of esophageal squamous cell carcinoma by regulating lipid metabolism. Int J Oncol 2025; 66:15. [PMID: 39821659 PMCID: PMC11753767 DOI: 10.3892/ijo.2025.5721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 12/06/2024] [Indexed: 01/19/2025] Open
Abstract
Solute carrier family 25 member 1 (SLC25A1) affects lipid metabolism and energy regulation in multiple types of tumor cell, affecting their proliferation and survival. To the best of our knowledge, however, the impact of SLC25A1 on the proliferation and survival of esophageal squamous cell carcinoma (ESCC) cells has yet to be explored. Here, SLC25A1 expression was detected in ESCC tissues and cell lines. SLC25A1 was silenced or blocked by lentivirus transfection or 2‑[(4‑chloro‑3‑nitrophenyl)sulfonylamino]benzoic acid in ESCC cells. To evaluate the impact of SLC25A1 on in vivo and in vitro proliferation, invasion and migration of ESCC cells, Cell Counting‑Kit, wound healing, colony formation, Transwell, EdU, flow cytometry, tumor xenograft in nude mice, lipid metabolism and energy metabolism detection assays were performed. Reverse transcription‑quantitative PCR and western blot analysis were performed to determine expression of downstream molecules and pathway proteins following the silencing and blockade of SLC25A1. SLC25A1 was significantly overexpressed in ESCC tissue and cell lines. The targeted silencing of SLC25A1 or inhibition of its protein led to a significant decrease in proliferative, invasive and migratory capabilities of ESCC cells, accompanied by increased apoptosis. Additionally, silencing of the SLC25A1 gene significantly inhibited xenograft tumor growth in vivo. The present results indicate that knockdown or blockade of SLC25A1 can significantly impede the malignant biological behavior of ESCC.
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Affiliation(s)
- Guoquan Zhang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
| | - Jingru Wu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
| | - Minghao Ji
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
| | - Xiangyan Liu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
| | - Mo Shi
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
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Tan L, Yang G, Zeng C, Zhang X. Case report: Watch-and-wait strategy in resectable esophageal cancer following neoadjuvant chemoimmunotherapy: a case series. Front Immunol 2025; 15:1502206. [PMID: 39835129 PMCID: PMC11743936 DOI: 10.3389/fimmu.2024.1502206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025] Open
Abstract
Neoadjuvant chemoimmunotherapy (NCIT) has improved pathological complete response and conferred survival benefits in patients with locally advanced esophageal cancer. However, surgical complications unrelated to the tumor continue to detract from patient outcomes. While the "watch-and-wait" strategy has been implemented in clinical complete responders following neoadjuvant therapy for rectal cancer, there is a lack of evidence supporting its practicability in esophageal cancer after NCIT. This pilot case series involves six clinical complete responders who deferred surgery under close surveillance after three or four cycles of neoadjuvant camrelizumab plus chemotherapy and who subsequently received camrelizumab as maintenance treatment. The primary observation measure of the series is event-free survival (EFS). Routine follow-up examinations included endoscopy, biopsy, contrast-enhanced computed tomography, and ultrasonography every 3-6 months. For patients who experienced local recurrence without metastasis, the salvage operation was the priority recommendation. As of September 5, 2024, the average follow-up duration was 124.4 weeks, with the average EFS reaching 134.7 weeks. No deaths or distant metastases were observed. Our findings suggest that responders to NCIT may be spared from esophagectomy. On the prerequisite of sufficient tumor regression during neoadjuvant cycles, immunotherapy may facilitate the continued eradication of residual disease in this series.
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Affiliation(s)
- Lingyu Tan
- Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Guozhen Yang
- Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chufeng Zeng
- Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xu Zhang
- Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Guangdong Esophageal Cancer Institute, Guangzhou, China
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Ye C, Xu C, Tang Y, Qi Y, Peng X, Wei G, Jiang L. A novel disulfidptosis-related LncRNA prognostic risk model: predicts the prognosis, tumor microenvironment and drug sensitivity in esophageal squamous cell carcinoma. BMC Gastroenterol 2024; 24:437. [PMID: 39604874 PMCID: PMC11603746 DOI: 10.1186/s12876-024-03530-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 11/21/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Disulfidptosis is a newly discovered type of cell death that differs from apoptosis, necrosis, ferroptosis and other death modes and is closely related to the occurrence and progression of tumors. However, the predictive potential and biological characteristics of disulfidptosis-related lncRNAs (DRGs-lncRNAs) in esophageal squamous cell carcinoma (ESCC) are unclear. METHODS RNA transcriptome data, clinical information and mutation data for ESCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation and Cox regression analyses were used to identify the DRGs-lncRNAs associated with overall survival (OS). LASSO regression analysis was used to construct the prognostic model. A nomogram was created to predict the prognosis of patients with ESCC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the signaling pathways associated with the model. TIMER, CIBERSORT, ESTIMATE and other methods were used to analyze immune infiltration, immune function, immune checkpoints and drug sensitivity. The tumor mutation burden (TMB) were assessed between different risk groups. Real-time polymerase chain reaction (RT‒PCR) was used to detect the expression of DRGs-lncRNAs in ESCC cell lines. RESULTS A total of 155 lncRNAs significantly associated with disulfidptosis were identified. Through univariate Cox regression analysis, LASSO regression analysis and multivariate Cox regression analysis, 9 lncRNAs with independent prognostic significance were selected, and a prognosis model was established. Survival analysis with the prognostic model revealed that there were obvious differences in survival between the high- and low-risk groups. Further analysis revealed that the immune microenvironment, immune infiltration, immune function, immune checkpoints, and drug sensitivity significantly differed between the high-risk and low-risk groups. Patients who exhibited both high risk and high tumor mutation burden (TMB) survived shorter, while those who fell into the low risk and low TMB categories survived longer. In addition, RT‒PCR analysis revealed differential expression of DRG lncRNAs between ESCC cell lines and esophageal epithelial cell lines. CONCLUSIONS We established a DRG-lncRNA prognostic model that can be used to predict the prognosis, tumor mutation burden, immune cell infiltration, and drug sensitivity of ECSS patients. The results of this study provide valuable insights into the understanding of ESCC and provide valuable assistance for the individualized treatment of ESCC patients.
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Affiliation(s)
- Chunlin Ye
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China
| | - Chuan Xu
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China
| | - Yongchao Tang
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China
| | - Yingcheng Qi
- Department of Gastroenterological Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Xiaoyue Peng
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China
| | - Guangxia Wei
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China.
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China.
| | - Lei Jiang
- Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China.
- Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China.
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Nanchang, Jiangxi, 330000, People's Republic of China.
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Yang H, Wang F, Hallemeier CL, Lerut T, Fu J. Oesophageal cancer. Lancet 2024; 404:1991-2005. [PMID: 39550174 DOI: 10.1016/s0140-6736(24)02226-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/16/2024] [Accepted: 10/07/2024] [Indexed: 11/18/2024]
Abstract
Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies.
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Affiliation(s)
- Hong Yang
- Department of Thoracic Surgery, Sun Ya University Cancer Center, Guangzhou, China; Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China
| | - Feng Wang
- Department of Medical Oncology, Sun Ya University Cancer Center, Guangzhou, China; Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | | | - Toni Lerut
- Department of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium
| | - Jianhua Fu
- Department of Thoracic Surgery, Sun Ya University Cancer Center, Guangzhou, China; Guangdong Provincial Clinical Research Center for Cancer, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China; Guangdong Esophageal Cancer Institute, Guangzhou, China.
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8
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Liu Y, Wang Y, Hu X, Wang X, Xue L, Pang Q, Zhang H, Ma Z, Deng H, Yang Z, Sun X, Men Y, Ye F, Men K, Qin J, Bi N, Zhang J, Wang Q, Hui Z. Multimodality deep learning radiomics predicts pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. Insights Imaging 2024; 15:277. [PMID: 39546168 PMCID: PMC11568088 DOI: 10.1186/s13244-024-01851-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 10/23/2024] [Indexed: 11/17/2024] Open
Abstract
OBJECTIVES This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). MATERIALS AND METHODS Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models' performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. RESULTS The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766-0.959), sensitivity of 88% (95% CI: 73.9-100), and specificity of 78.4% (95% CI: 63.6-90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. CONCLUSION A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. CRITICAL RELEVANCE STATEMENT Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. KEY POINTS After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer.
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Affiliation(s)
- Yunsong Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Xinyang Hu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingsong Pang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Huan Zhang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Zeliang Ma
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Heping Deng
- Department of Diagnostic Radiology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Zhaoyang Yang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xujie Sun
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Men
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Ye
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kuo Men
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Qin
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Zhang
- Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Engineering Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
| | - Qifeng Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
| | - Zhouguang Hui
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Wu H, Liu Q, Li J, Leng X, He Y, Liu Y, Zhang X, Ouyang Y, Liu Y, Liang W, Xu C. Tumor-Resident Microbiota-Based Risk Model Predicts Neoadjuvant Therapy Response of Locally Advanced Esophageal Squamous Cell Carcinoma Patients. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2309742. [PMID: 39268829 PMCID: PMC11538710 DOI: 10.1002/advs.202309742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 07/11/2024] [Indexed: 09/15/2024]
Abstract
Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota-based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease-free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP-plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP-plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis.
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Affiliation(s)
- Hong Wu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
| | - Qianshi Liu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
| | - Jingpei Li
- Thoracic Surgery DepartmentThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510230P. R. China
| | - Xuefeng Leng
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
| | - Yazhou He
- Department of OncologyWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan610041P. R. China
| | - Yiqiang Liu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
| | - Xia Zhang
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Institute of Pathology and Southwest Cancer CenterMinistry of Education of ChinaSouthwest HospitalThird Military Medical University (Army Medical University) and Key Laboratory of Tumor ImmunopathologyChongqing400038P. R. China
| | - Yujie Ouyang
- Acupuncture and Massage CollegeChengdu University of Traditional Chinese MedicineChengduSichuan610072P. R. China
| | - Yang Liu
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
| | - Wenhua Liang
- Thoracic Surgery DepartmentThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510230P. R. China
| | - Chuan Xu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
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Lu Z, Li Y, Hu W, Cao Y, Lv X, Jia X, Shen S, Zhao J, Xu C. Radiomics nomogram combined with clinical factors for predicting pathological complete response in resectable esophageal squamous cell carcinoma. Front Oncol 2024; 14:1347650. [PMID: 39544301 PMCID: PMC11560869 DOI: 10.3389/fonc.2024.1347650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 10/03/2024] [Indexed: 11/17/2024] Open
Abstract
Introduction Predicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy. Methods We retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model's performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort. Results We enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil-Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram's superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model. Conclusion The nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients.
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Affiliation(s)
| | | | | | | | | | | | | | - Jun Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow
University, Suzhou, China
| | - Chun Xu
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow
University, Suzhou, China
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11
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Wong R, Anderson B, Bashir B, Bateman J, Chalchal H, Davies J, Dehmoobed A, Geller G, Ghose A, Gill S, Gordon V, Green S, Hebbard P, Iqbal M, Ji S, Karachiwala H, Kidane B, Kim C, Kosyachkova E, Krahn M, Krishnan T, Kristjanson M, Lee S, Lee-Ying R, Lelond S, Liu HW, Meyers D, Mulder K, Paul J, Planincic E. Report from the 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Gastric and Gastroesophageal Cancers, Winnipeg, Manitoba, 26-27 October 2023. Curr Oncol 2024; 31:5987-6006. [PMID: 39451751 PMCID: PMC11505746 DOI: 10.3390/curroncol31100447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/20/2024] [Accepted: 09/21/2024] [Indexed: 10/26/2024] Open
Abstract
The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26-27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers.
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Affiliation(s)
- Ralph Wong
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Brady Anderson
- Western Manitoba Cancer Center, Brandon, MB R7A 5M8, Canada;
| | - Bashir Bashir
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | | | - Haji Chalchal
- Allan Blair Cancer Centre, Regina, SK S4T 7T1, Canada;
| | - Janine Davies
- BC Cancer Centre, Vancouver, BC V5Z 4E6, Canada; (J.D.); (S.G.); (T.K.)
| | - Anahita Dehmoobed
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | | | - Abhijit Ghose
- Chinook Regional Hospital, Lethbridge, AB T1J 1W5, Canada
| | - Sharlene Gill
- BC Cancer Centre, Vancouver, BC V5Z 4E6, Canada; (J.D.); (S.G.); (T.K.)
| | - Vallerie Gordon
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Susan Green
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Pamela Hebbard
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | | | - Shuying Ji
- Shared Health Manitoba, Winnipeg, MB R2N 0E2, Canada;
| | - Hatim Karachiwala
- Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (H.K.); (R.L.-Y.)
| | - Biniam Kidane
- Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3A 1R9, Canada;
| | - Christina Kim
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | | | - Marianne Krahn
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Tharani Krishnan
- BC Cancer Centre, Vancouver, BC V5Z 4E6, Canada; (J.D.); (S.G.); (T.K.)
| | - Mark Kristjanson
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Sangjune Lee
- Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada;
| | - Richard Lee-Ying
- Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (H.K.); (R.L.-Y.)
| | - Stephanie Lelond
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Hong-Wei Liu
- Central Alberta Cancer Center, Red Deer, AB T4N 6R2, Canada;
| | - Daniel Meyers
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Karen Mulder
- Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada;
| | - James Paul
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
| | - Elvira Planincic
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (B.B.); (A.D.); (V.G.); (S.G.); (P.H.); (M.K.); (M.K.); (S.L.); (D.M.); (E.P.); (J.P.)
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Zhang X, Lin Z, Feng Y, Lin Z, Tao K, Zhang T, Lan X. Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [ 68Ga]Ga-FAPI-04 PET, [ 18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology. J Nucl Med 2024; 65:1548-1556. [PMID: 39353648 DOI: 10.2967/jnumed.124.267581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 08/13/2024] [Indexed: 10/04/2024] Open
Abstract
Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter's sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.
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Affiliation(s)
- Xiao Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and
| | - Yuan Feng
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Zhaoguo Lin
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and
| | - Xiaoli Lan
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
- Key Laboratory of Biological Targeted Therapy, Ministry of Education, Wuhan, China
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Ye G, Wu G, Qi Y, Li K, Wang M, Zhang C, Li F, Wee L, Dekker A, Han C, Liu Z, Liao Y, Shi Z. Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study. J Immunother Cancer 2024; 12:e009348. [PMID: 39231545 PMCID: PMC11409329 DOI: 10.1136/jitc-2024-009348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2024] [Indexed: 09/06/2024] Open
Abstract
OBJECTIVES Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers. METHODS This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023. Deep learning features were extracted from both non-contrast enhanced and contrast enhanced CT scans to construct the predictive models (LUNAI-uCT model and LUNAI-eCT model), respectively. After the feature fusion of these two types of features, a fused model (LUNAI-fCT model) was constructed. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. SHapley Additive exPlanations analysis was used to quantify the impact of CT imaging features on model prediction. To gain insights into how our model makes predictions, we employed Gradient-weighted Class Activation Mapping to generate saliency heatmaps. RESULTS The training and validation datasets included 113 patients from Center A at the 8:2 ratio, and the test dataset included 112 patients (Center B n=73, Center C n=20, Center D n=19). In the test dataset, the LUNAI-uCT, LUNAI-eCT, and LUNAI-fCT models achieved AUCs of 0.762 (95% CI 0.654 to 0.791), 0.797 (95% CI 0.724 to 0.844), and 0.866 (95% CI 0.821 to 0.883), respectively. CONCLUSIONS By extracting deep learning features from contrast enhanced and non-contrast enhanced CT, we constructed the LUNAI-fCT model as an imaging biomarker, which can non-invasively predict pathological complete response in neoadjuvant immunochemotherapy for NSCLC.
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Affiliation(s)
- Guanchao Ye
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Department of Thoracic Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China
| | - Guangyao Wu
- Department of Radiology, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China
| | - Yu Qi
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Kuo Li
- Department of Thoracic Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China
| | - Mingliang Wang
- Department of Thoracic Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Chunyang Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Feng Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Leonard Wee
- Clinical Data Science, Faculty of Health Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
- Department of Radiation Oncology (Maastro), GROW School of Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Andre Dekker
- Department of Radiation Oncology (Maastro), GROW School of Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Chu Han
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
- Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zaiyi Liu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
| | - Yongde Liao
- Department of Thoracic Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China
| | - Zhenwei Shi
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
- Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
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14
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Chen M, Qi Y, Zhang S, Du Y, Cheng H, Gao S. Screening of genes related to programmed cell death in esophageal squamous cell carcinoma and construction of prognostic model based on transcriptome analysis. Expert Rev Anticancer Ther 2024; 24:905-915. [PMID: 38975629 DOI: 10.1080/14737140.2024.2377184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 06/19/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVES To screen programmed cell death (PCD)-related genes in esophageal squamous cell carcinoma (ESCC) based on transcriptomic data and to explore its clinical value. METHODS Differentially expressed PCD genes (DEPCDGs) were screened from ESCC transcriptome and clinical data in TCGA database. Univariate COX and LASSO COX were performed on prognostically DEPCDGs in ESCC to develop prognostic model. Differences in immune cell infiltration in different RiskScore groups were determined by ssGSEA and CIBERSORT. The role of RiskScore in immunotherapy response was explored using Tumor Immune Dysfunction and Exclusion (TIDE) and IMvigor210 cohorts. RESULTS Fourteen DEPCDGs associated with prognosis were tapped in ESCC. These DEPCDGs form a RiskScore with good predictive performance for prognosis. RiskScore demonstrated excellent prediction accuracy in three data sets. The abundance of M2 macrophages and Tregs was higher in the high RiskScore group, and the abundance of M1 macrophages was higher in the low RiskScore group. The RiskScore also showed good immunotherapy sensitivity. RT-qPCR analysis showed that AUP1, BCAP31, DYRK2, TAF9 and UBQLN2 were higher expression in KYSE-150 cells. Knockdown BCAP31 inhibited migration and invasion. CONCLUSION A prognostic risk model can predict prognosis of ESCC and may be a useful biomarker for risk stratification and immunotherapy assessment.
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Affiliation(s)
- Min Chen
- School of Information Engineering, Henan University of Science and Technology, Luoyang, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
| | - Yijun Qi
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
| | - Shenghua Zhang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
| | - Yubo Du
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
| | - Haodong Cheng
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
| | - Shegan Gao
- School of Information Engineering, Henan University of Science and Technology, Luoyang, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- Cancer Hospital, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
- College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China
- Medical College, Henan University of Science and Technology, Luoyang, China
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15
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Li Y, Su X, Shang Y, Liu H, Wang W, Zhang A, Shi G. Comparative evaluation of imaging methods for prognosis assessment in esophageal squamous cell carcinoma: focus on diffusion-weighted magnetic resonance imaging, computed tomography and esophagography. Front Oncol 2024; 14:1397266. [PMID: 39026975 PMCID: PMC11256006 DOI: 10.3389/fonc.2024.1397266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 06/17/2024] [Indexed: 07/20/2024] Open
Abstract
Objective To identify the most sensitive imaging examination method to evaluate the prognosis of esophageal squamous cell carcinoma (ESCC). Materials and methods Thirty patients with esophageal squamous cell carcinoma (ESCC) participated in the study and underwent chemoradiotherapy (CRT). They were divided into two groups based on their survival status: the survival group and non-survival group. The diagnostic tests were utilized to determine the most effective imaging examination method for assessing the prognosis. Results 1. There were no significant differences in tumor length shown on esophagography or computed tomography (CT) or the maximal esophageal wall thickness shown on CT at the specified time points between the two groups. 2. The tumor length on diffusion-weighted imaging (DWI) in the survival group was significantly lower than in the non-survival group at the end of the sixth week of treatment (P=0.001). The area under the ROC curve was 0.840 (P=0.002), and the diagnostic efficiency was moderately accurate. 3. The apparent diffusion coefficient (ADC) values of the survival group were significantly higher than those in the non-survival group at the end of the fourth week and sixth week of treatment (both P<0.001). Areas under the curve were 0.866 and 0.970, with P values of 0.001 and <0.001 and good diagnostic accuracy. Cox regression analyses indicated the ADC at the end of the sixth week of treatment was an independent risk factor. Conclusions Compared with esophagography and CT, DW-MRI has certain advantages in predicting the prognosis of ESCC.
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Affiliation(s)
- Yang Li
- Department of Computed Tomography and Magnetic Resonance Imaging, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaohua Su
- Department of Oncology, Hebei General Hospital, Shijiazhuang, China
| | - Yuguang Shang
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hui Liu
- Department of Computed Tomography and Magnetic Resonance Imaging, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weishuai Wang
- CS Service AP, Siemens Healthineers Digital Health Technology (Shanghai) Co., Ltd. Beijing Branch, Beijing, China
| | - Andu Zhang
- Department of Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Gaofeng Shi
- Department of Computed Tomography and Magnetic Resonance Imaging, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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16
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Chen KN. ASO Author Reflections: The Challenging Journey from cCR to pCR After Neoadjuvant Treatment for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2024; 31:4317-4320. [PMID: 38366184 DOI: 10.1245/s10434-024-15035-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 01/25/2024] [Indexed: 02/18/2024]
Affiliation(s)
- Ke-Neng Chen
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Thoracic Surgery of Department, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
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17
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Gao LR, Zhang J, Huang N, Deng W, Ni W, Xiao Z, Liu M. Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2024; 25:6082. [PMID: 38892269 PMCID: PMC11172887 DOI: 10.3390/ijms25116082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/24/2024] [Accepted: 05/26/2024] [Indexed: 06/21/2024] Open
Abstract
We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.
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Affiliation(s)
- Lin-Rui Gao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Jiajun Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (J.Z.); (N.H.)
| | - Ning Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (J.Z.); (N.H.)
| | - Wei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Wenjie Ni
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Zefen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; (L.-R.G.); (W.D.); (W.N.)
| | - Mei Liu
- Laboratory of Cell and Molecular Biology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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18
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Wu H, Deng M, Xue D, Guo R, Zhang C, Gao J, Li H. PD-1/PD-L1 inhibitors for early and middle stage microsatellite high-instability and stable colorectal cancer: a review. Int J Colorectal Dis 2024; 39:83. [PMID: 38809459 PMCID: PMC11136714 DOI: 10.1007/s00384-024-04654-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/22/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important immune checkpoint molecules that contribute to tumor immune evasion. However, the main treatment modalities for patients with early and intermediate stage colorectal cancer (CRC) are surgery, and the role of PD-1/PD-L1 inhibitors in these patients is not yet clear. Therefore, this study aims to review the treatment progress of PD-1/PD-L1 inhibitors for early- and intermediate-stage microsatellite high-instability (MSI-H) and stable (MSS) colorectal cancer, in order to provide more options for patients with early- and intermediate-stage colorectal cancer. MATERIALS AND METHODS A scoping review of clinical trial registries ( Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on PD-1/PD-L1 Inhibitors for early and middle-stage MSI-H and MSS CRC was done up to March 2024. RESULTS A total of 19 trials related to early to mid-stage MSH-I or MSS CRC were included. Among them, 6 trials are in recruiting status, 3 trials are in active, not recruiting status, 3 trials are completed, 1 trial is terminated, and 1 trial is unknown. Of these, 9 trials involve MSI-H type CRC, and 10 trials involve MSS type CRC. Preclinical phase I/II trials are predominant, with only 3 clinical phase III trials. In trials related to MSI-H type CRC, 4 studies involve PD-1/PD-L1 inhibitors combined with neoadjuvant therapy, and 5 studies involve combination therapy. In trials related to MSS type CRC, 3 studies involve PD-1/PD-L1 inhibitors combined with targeted therapy, 2 studies involve PD-1/PD-L1 inhibitors combined with chemotherapy, 1 study involves PD-1/PD-L1 inhibitor combined immunotherapy, 1 study involves PD-1/PD-L1 inhibitors combined with bacterial therapy, and 3 studies involve PD-1/PD-L1 inhibitors combined with comprehensive therapy. As for primary outcome measures, 4 trials select pathological complete response rates, 3 trials select progression-free survival rate, 3 trials select objective response rate, 3 trials select overall survival rate, 4 trials select disease-free survival rate, 1 trial selects clinical complete response rate, and 1 trial selects percentage of participants with a dose-limiting toxicity. CONCLUSION For early- and middle-stage MSI-H and MSS CRC, PD-1/PD-L1 inhibitors have shown some therapeutic efficacy, as evidenced by phase I/II studies. However, contemporary trial designs exhibit heterogeneity, with relatively few inclusion criteria, the use of various drug combinations and regimens, and significant variations in reported endpoints. Nevertheless, more double-arm, multicenter, randomized controlled trials are still needed to confirm the efficacy of immunotherapy.
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Affiliation(s)
- Huiming Wu
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Min Deng
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Dingwen Xue
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Renkai Guo
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Chenyu Zhang
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Jiaqi Gao
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Huiyu Li
- Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
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19
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Bandidwattanawong C. Multi-disciplinary management of esophageal carcinoma: Current practices and future directions. Crit Rev Oncol Hematol 2024; 197:104315. [PMID: 38462149 DOI: 10.1016/j.critrevonc.2024.104315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 01/30/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Esophageal cancer in one of the most malignant and hard-to-treat cancers. Esophageal squamous carcinoma (ESCC) is most common in Asian countries, whereas adenocarcinoma at the esophago-gastric junction (EGJ AC) is more prevalent in the Western countries. Due to differences in both genetic background and response to chemotherapy and radiotherapy, both histologic subtypes need different paradigms of management. Since the landmark CROSS study has demonstrated the superior survival benefit of tri-modality including neoadjuvant chemoradiotherapy prior to esophagectomy, the tri-modality becomes the standard of care; however, it is suitable for a highly-selected patient. Tri-modality should be offered for every ESCC patient, if a patient is fit for surgery with adequate cardiopulmonary reserve, regardless of ages. Definitive chemoradiotherapy remains the best option for a patient who is not a surgical candidate or declines surgery. On the contrary, owing to doubtful benefits of radiotherapy with potentially more toxicities related to radiotherapy in EGJ AC, either neoadjuvant chemotherapy or peri-operative chemotherapy would be more preferable in an EGJ AC patient. In case of very locally advanced disease (cT4b), the proper management is more challenging. Even though, palliative care is the safe option, multi-modality therapy with curative intent like neoadjuvant chemotherapy with conversion surgery may be worthwhile; however, it should be suggested on case-by-case basis.
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Affiliation(s)
- Chanyoot Bandidwattanawong
- Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Thailand.
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20
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Zhang GL, Zhu QK, Ma TY, Weng CG, Zhang DD, Zeng H, Wang T, Gao F, Mi LL, Wang R. Clinical study of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma. Dis Esophagus 2024; 37:doad073. [PMID: 38189470 DOI: 10.1093/dote/doad073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Herein, we aimed to evaluate the efficacy and safety of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (OSCC). Fifty-one patients with OSCC, treated from July 2020 to October 2022, were analyzed. Of them, 41 patients underwent surgery 4-8 weeks after undergoing two cycles of camrelizumab (200 mg IV Q3W) combined with docetaxel (75 mg/m2 IV Q3W) and carboplatin (area under the curve = 5-6 IV Q3W). The primary endpoint was the pathological complete response rate. All 51 patients (100%) experienced treatment-related grades 1-2 adverse events, and 2 patients (3.9%) experienced grade 4 events (including elevated alanine transaminase/aspartate transferase levels and Guillain-Barre syndrome). Fifty patients were evaluated for the treatment efficacy. Of them, 13 achieved complete response, and the objective response rate was 74%. Only 41 patients underwent surgical treatment. The pathological complete response rate was 17.1%, the major pathological response rate was 63.4%, and the R0 resection rate was 100%. Approximately 22% of the patients had tumor regression grades 0. Eight patients (19.5%) developed surgery-related complications. The median follow-up time was 18 months (range: 3-29 months). Four patients experienced disease progression, while four died. The median disease-free survival and overall survival were not reached. Camrelizumab combined with docetaxel and carboplatin is an effective and safe neoadjuvant treatment for locally advanced OSCC. This regimen may afford a potential strategy to treat patients with locally advanced OSCC.
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Affiliation(s)
- Guo-Liang Zhang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Qi-Kun Zhu
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Tian-You Ma
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Chen-Gang Weng
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Dan-Dan Zhang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hui Zeng
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Tao Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Feng Gao
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Li-Li Mi
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Rui Wang
- Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
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21
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Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA. Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus. United European Gastroenterol J 2024; 12:399-411. [PMID: 38284661 PMCID: PMC11017771 DOI: 10.1002/ueg2.12523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 11/21/2023] [Indexed: 01/30/2024] Open
Abstract
Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.
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Affiliation(s)
- Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus OsterholzOsterholz‐ScharmbeckGermany
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von MagenDarm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro‐Liga) e. V.GiessenGermany
| | - Ines Gockel
- Klinik für Viszeral‐, Transplantations‐, Thorax‐ und GefäßchirurgieLeipzigGermany
| | | | - Arnulf Hölscher
- Contilia Zentrum für SpeiseröhrenerkrankungenElisabeth Krankenhaus EssenEssenGermany
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für GastroenterologieVerdauungs‐ und StoffwechselkrankheitenBerlinGermany
| | | | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle EndoskopieKrankenhaus Barmherzige BrüderRegensburgGermany
| | - Michael Stahl
- Klinik für Internistische Onkologie & Onkologische PalliativmedizinEvang. Kliniken Essen‐MitteEssenGermany
| | - Udo Vanhoefer
- Klinik für Hämatologie und OnkologieKath. MarienkrankenhausHamburgGermany
| | - Matthias P. A. Ebert
- Medizinische Fakultät MannheimII. Medizinische KlinikUniversitätsmedizinUniversität HeidelbergMannheimGermany
- DKFZ‐Hector Krebsinstitut an der Universitätsmedizin MannheimMannheimGermany
- Molecular Medicine Partnership UnitEMBLHeidelbergGermany
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22
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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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23
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Liu G, Chen T, Zhang X, Hu B, Yu J. Nomogram for predicting pathologic complete response to neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Med 2024; 13:e7075. [PMID: 38477511 DOI: 10.1002/cam4.7075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 02/12/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
PURPOSE A pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in up to 40% of the patients with esophageal squamous cell carcinoma (ESCC). No nomogram has been constructed for the prediction of pCR for patients whose primary chemotherapy was a taxane-based regimen. The aim is to identify characteristics associated with a pCR through analyzing multiple pre- and post-nCRT variables and to develop a nomogram for the prediction of pCR for these patients by integrating clinicopathological characteristics and hematological biomarkers. MATERIALS AND METHODS We analyzed 293 patients with ESCC who underwent nCRT followed by esophagectomy. Clinicopathological factors, hematological parameters before nCRT, and hematotoxicity during nCRT were collected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for pCR. A nomogram model was built and evaluated for both discrimination and calibration. RESULTS After surgery, 37.88% of the study patients achieved pCR. Six variables were included in the nomogram: sex, cN stage, chemotherapy regimen, duration of nCRT, pre-nCRT neutrophil-to-lymphocyte ratio (NLR), and pre-nCRT platelet-to-lymphocyte ratio (PLR). The nomogram indicated good accuracy and consistency in predicting pCR, with a C-index of 0.743 (95% confidence interval: 0.686, 0.800) and a p value of 0.600 (>0.05) in the Hosmer-Lemeshow goodness-of-fit test. CONCLUSIONS Female, earlier cN stage, duration of nCRT (< 62 days), chemotherapy regimen of taxane plus platinum, pre-nCRT NLR (≥2.199), and pre-nCRT PLR (≥99.302) were significantly associated with a higher pCR in ESCC patients whose primary chemotherapy was a taxane-based regimen for nCRT. A nomogram was developed and internally validated, showing good accuracy and consistency.
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Affiliation(s)
- Guihong Liu
- Department of Radiotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tao Chen
- Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xin Zhang
- Department of Radiotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Binbin Hu
- Department of Radiotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiayun Yu
- Department of Radiotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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24
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De Pasqual CA, Weindelmayer J, Gervasi MC, Torroni L, Pavarana M, Cenzi D, Togliani T, Rossi R, Giacopuzzi S. Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma. Br J Surg 2024; 111:znae036. [PMID: 38415879 DOI: 10.1093/bjs/znae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 11/30/2023] [Accepted: 01/29/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. METHODS Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. RESULTS The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. CONCLUSION Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.
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Affiliation(s)
- Carlo A De Pasqual
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Jacopo Weindelmayer
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Maria C Gervasi
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
| | - Lorena Torroni
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | | | - Daniela Cenzi
- Department of Radiology, OCM Hospital of Verona, Verona, Italy
| | - Thomas Togliani
- Gastroenterology and Digestive Endoscopy Unit, University of Verona, Verona, Italy
| | - Roberto Rossi
- Department of Radiation Oncology, University of Verona, Verona, Italy
| | - Simone Giacopuzzi
- Department of General and Upper Gastrointestinal Surgery, University of Verona, Verona, Italy
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Liu Y, Wang Y, Wang X, Xue L, Zhang H, Ma Z, Deng H, Yang Z, Sun X, Men Y, Ye F, Men K, Qin J, Bi N, Wang Q, Hui Z. MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study. Cancer Imaging 2024; 24:16. [PMID: 38263134 PMCID: PMC10804642 DOI: 10.1186/s40644-024-00659-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 01/10/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.
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Affiliation(s)
- Yunsong Liu
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Yi Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No.55.Section 4, South Renmin Road, Chengdu, 610042, China
| | - Xin Wang
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Liyan Xue
- Department of Pathology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Huan Zhang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No.55.Section 4, South Renmin Road, Chengdu, 610042, China
| | - Zeliang Ma
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Heping Deng
- Department of Diagnostic Radiology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No.55.Section 4, South Renmin Road, Chengdu, China
| | - Zhaoyang Yang
- Department of Pathology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Xujie Sun
- Department of Pathology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Yu Men
- Department of VIP Medical Services & Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, 100021, China
| | - Feng Ye
- Department of Diagnostic Radiology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Kuo Men
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Jianjun Qin
- Department of Thoracic Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, China
| | - Qifeng Wang
- Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No.55.Section 4, South Renmin Road, Chengdu, 610042, China.
| | - Zhouguang Hui
- Department of VIP Medical Services & Radiation Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli #17, Chaoyang District, Beijing, 100021, China.
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Gao D, Tan BG, Chen XQ, Zhou C, Ou J, Guo WW, Zhou HY, Li R, Zhang XM, Chen TW. Contrast-enhanced CT radiomics features to preoperatively identify differences between tumor and proximal tumor-adjacent and tumor-distant tissues of resectable esophageal squamous cell carcinoma. Cancer Imaging 2024; 24:11. [PMID: 38243339 PMCID: PMC10797955 DOI: 10.1186/s40644-024-00656-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/03/2024] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND Esophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence. METHODS A total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy. RESULTS With the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively. CONCLUSION CECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.
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Affiliation(s)
- Dan Gao
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
- Department of Radiology, Medical Center Hospital of Qionglai City, 172# Xinglin Road, Linqiong District, Chengdu, 611530, Sichuan, China
| | - Bang-Guo Tan
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
- Department of Radiology, Panzhihua Central Hospital, 34# Yikang Street, East District, Panzhihua, 617067, Sichuan, China
| | - Xiao-Qian Chen
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Chuanqinyuan Zhou
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Jing Ou
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Wen-Wen Guo
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Hai-Ying Zhou
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Rui Li
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Xiao-Ming Zhang
- Medical Imaging Key Laboratory of Sichuan Province, and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Tian-Wu Chen
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Rd, Yuzhong District, Chongqing, 400010, China.
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Li K, Zhang S, Hu Y, Cai A, Ao Y, Gong J, Liang M, Yang S, Chen X, Li M, Tian J, Shan H. Radiomics Nomogram with Added Nodal Features Improves Treatment Response Prediction in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter Study. Ann Surg Oncol 2023; 30:8231-8243. [PMID: 37755566 DOI: 10.1245/s10434-023-14253-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/22/2023] [Indexed: 09/28/2023]
Abstract
OBJECTIVE We aimed to develop and validate a radiomics nomogram and determine the value of radiomic features from lymph nodes (LNs) for predicting pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS In this multicenter retrospective study, eligible participants who had undergone NCRT followed by radical esophagectomy were consecutively recruited. Three radiomics models (modelT, modelLN, and modelTLN) based on tumor and LN features, alone and combined, were developed in the training cohort. The radiomics nomogram was developed by incorporating the prediction value of the radiomics model and clinicoradiological risk factors using multivariate logistic regression, and was evaluated using the receiver operating characteristic curve, validated in two external validation cohorts. RESULTS Between October 2011 and December 2018, 116 patients were included in the training cohort. Between June 2015 and October 2020, 51 and 27 patients from two independent hospitals were included in validation cohorts 1 and 2, respectively. The radiomics modelTLN performed better than the radiomics modelT for predicting pCR. The radiomics nomogram incorporating the predictive value of the radiomics modelTLN and heterogeneous after NCRT outperformed the clinicoradiological model, with an area under the curve (95% confidence interval) of 0.833 (0.765-0.894) versus 0.764 (0.686-0.833) [p = 0.088, DeLong test], 0.824 (0.718-0.909) versus 0.692 (0.554-0.809) [p = 0.012], and 0.902 (0.794-0.984) versus 0.696 (0.526-0.857) [p = 0.024] in all three cohorts. CONCLUSIONS Radiomic features from LNs could provide additional value for predicting pCR in ESCC patients, and the radiomics nomogram provided an accurate prediction of pCR, which might aid treatment decision.
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Affiliation(s)
- Kunwei Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
- Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
| | - Shuaitong Zhang
- School of Medical Technology, Beijing Institute of Technology, Beijing, People's Republic of China
| | - Yi Hu
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangdong Esophageal Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China
| | - Aiqun Cai
- Department of Radiology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
| | - Yong Ao
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China
| | - Jun Gong
- Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
| | - Mingzhu Liang
- Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
| | - Songlin Yang
- Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
| | - Xiangmeng Chen
- Department of Radiology, Jiangmen Central Hospital, Jiangmen, Guangdong Province, People's Republic of China
| | - Man Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China.
- Key Laboratory of Big Data-Based Precision Medicine, Beihang University, Ministry of Industry and Information Technology, Beijing, People's Republic of China.
| | - Hong Shan
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.
- Department of Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.
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28
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Yap WK, Hsiao IT, Yap WL, Tsai TY, Lu YA, Yang CK, Peng MT, Su EL, Cheng SC. A Radiotherapy Dose Map-Guided Deep Learning Method for Predicting Pathological Complete Response in Esophageal Cancer Patients after Neoadjuvant Chemoradiotherapy Followed by Surgery. Biomedicines 2023; 11:3072. [PMID: 38002072 PMCID: PMC10669191 DOI: 10.3390/biomedicines11113072] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/28/2023] [Accepted: 11/03/2023] [Indexed: 11/26/2023] Open
Abstract
Esophageal cancer is a deadly disease, and neoadjuvant chemoradiotherapy can improve patient survival, particularly for patients achieving a pathological complete response (ypCR). However, existing imaging methods struggle to accurately predict ypCR. This study explores computer-aided detection methods, considering both imaging data and radiotherapy dose variations to enhance prediction accuracy. It involved patients with node-positive esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery, with data collected from 2014 to 2017, randomly split into five subsets for 5-fold cross-validation. The algorithm DCRNet, an advanced version of OCRNet, integrates RT dose distribution into dose contextual representations (DCR), combining dose and pixel representation with ten soft regions. Among the 80 enrolled patients (mean age 55.68 years, primarily male, with stage III disease and middle-part lesions), the ypCR rate was 28.75%, showing no significant demographic or disease differences between the ypCR and non-ypCR groups. Among the three summarization methods, the maximum value across the CTV method produced the best results with an AUC of 0.928. The HRNetV2p model with DCR performed the best among the four backbone models tested, with an AUC of 0.928 (95% CI, 0.884-0.972) based on 5-fold cross-validation, showing significant improvement compared to other models. This underscores DCR-equipped models' superior AUC outcomes. The study highlights the potential of dose-guided deep learning in ypCR prediction, necessitating larger, multicenter studies to validate the results.
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Affiliation(s)
- Wing-Keen Yap
- Department of Radiation Oncology, Proton and Radiation Therapy Center, Chang Gung Memorial Hospital—Linkou Medical Center, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
| | - Ing-Tsung Hsiao
- Department of Medical Imaging and Radiological Sciences, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
| | - Wing-Lake Yap
- Department of Post Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tsung-You Tsai
- Department of Otolaryngology—Head and Neck Surgery, Chang Gung Memorial Hospital—Linkou Medical Center, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
| | - Yi-An Lu
- Department of Otolaryngology—Head and Neck Surgery, Chang Gung Memorial Hospital—Linkou Medical Center, 5 Fu-Shin Street, Kwei-Shan, Taoyuan 333, Taiwan
| | - Chan-Keng Yang
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - Meng-Ting Peng
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou Branch, Chang Gung University College of Medicine, Taoyuan 333, Taiwan
| | - En-Lin Su
- Department of School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Lin Y, Liang HW, Liu Y, Pan XB. Nivolumab adjuvant therapy for esophageal cancer: a review based on subgroup analysis of CheckMate 577 trial. Front Immunol 2023; 14:1264912. [PMID: 37860010 PMCID: PMC10582756 DOI: 10.3389/fimmu.2023.1264912] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/18/2023] [Indexed: 10/21/2023] Open
Abstract
Esophageal cancer is the sixth most common cancer worldwide. Approximately 50% of patients have locally advanced disease. The CROSS and NEOCRTEC5010 trials have demonstrated that neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with resectable disease. However, a pathological complete response is frequently not achieved, and most patients have a poor prognosis. The CheckMate 577 trial demonstrates that nivolumab adjuvant therapy improves disease-free survival in patents without a pathological complete response. However, there are still numerous clinical questions of concern that remain controversial based on the results of the subgroup analysis. In this review, we aim to offer constructive suggestions addressing the clinical concerns raised in the CheckMate 577 trial.
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Affiliation(s)
- Yan Lin
- Department of Gastroenterology, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Huan-Wei Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Yang Liu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Xin-Bin Pan
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
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30
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den Boer R, Siang KNW, Yuen M, Borggreve A, Defize I, van Lier A, Ruurda J, van Hillegersberg R, Mook S, Meijer G. A robust semi-automatic delineation workflow using denoised diffusion weighted magnetic resonance imaging for response assessment of patients with esophageal cancer treated with neoadjuvant chemoradiotherapy. Phys Imaging Radiat Oncol 2023; 28:100489. [PMID: 37822533 PMCID: PMC10562188 DOI: 10.1016/j.phro.2023.100489] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 08/24/2023] [Accepted: 08/25/2023] [Indexed: 10/13/2023] Open
Abstract
Background and Purpose Diffusion weighted magnetic resonance imaging (DW-MRI) can be prognostic for response to neoadjuvant chemotherapy (nCRT) in patients with esophageal cancer. However, manual tumor delineation is labor intensive and subjective. Furthermore, noise in DW-MRI images will propagate into the corresponding apparent diffusion coefficient (ADC) signal. In this study a workflow is investigated that combines a denoising algorithm with semi-automatic segmentation for quantifying ADC changes. Materials and Methods Twenty patients with esophageal cancer who underwent nCRT before esophagectomy were included. One baseline and five weekly DW-MRI scans were acquired for every patient during nCRT. A self-supervised learning denoising algorithm, Patch2Self, was used to denoise the DWI-MRI images. A semi-automatic delineation workflow (SADW) was next developed and compared with a manually adjusted workflow (MAW). The agreement between workflows was determined using the Dice coefficients and Brand Altman plots. The prognostic value of ADCmean increases (%/week) for pathologic complete response (pCR) was assessed using c-statistics. Results The median Dice coefficient between the SADW and MAW was 0.64 (interquartile range 0.20). For the MAW, the c-statistic for predicting pCR was 0.80 (95% confidence interval (CI):0.56-1.00). The SADW showed a c-statistic of 0.84 (95%CI:0.63-1.00) after denoising. No statistically significant differences in c-statistics were observed between the workflows or after applying denoising. Conclusions The SADW resulted in non-inferior prognostic value for pCR compared to the more laborious MAW, allowing broad scale applications. The effect of denoising on the prognostic value for pCR needs to be investigated in larger cohorts.
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Affiliation(s)
- Robin den Boer
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Kelvin Ng Wei Siang
- Erasmus MC Cancer Institute, University Medical Center Rotterdam, Department of Radiotherapy, Rotterdam, The Netherlands
- Holland Proton Therapy Center, Department of Medical Physics & Informatics, Delft, The Netherlands
| | - Mandy Yuen
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Alicia Borggreve
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Ingmar Defize
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Astrid van Lier
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Jelle Ruurda
- University Medical Center Utrecht, Department of Surgery, Utrecht, The Netherlands
| | | | - Stella Mook
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
| | - Gert Meijer
- University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands
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Donisi G, Nappo G, Pacilli M, Capretti GL, Spaggiari P, Sollai M, Bozzarelli S, Zerbi A. Pathologic tumor response to neoadjuvant therapy in resected pancreatic cancer: does it affect prognosis? Updates Surg 2023; 75:1497-1508. [PMID: 37578734 DOI: 10.1007/s13304-023-01628-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 08/04/2023] [Indexed: 08/15/2023]
Abstract
Neoadjuvant therapy (NAT) + surgical resection for pancreatic cancer (PC) has gained consensus in recent years. Pathological response (PR) is generally assessed according to the College of American Pathologists grading system, ranging from 0 (complete response) to 3 (no response). The aim of our study is to evaluate the PR in a series of resections for PC after NAT and its prognostic implication. 112 patients undergone NAT and resection for PC between 2011 and 2020 were retrospectively evaluated. PR was 0/1, 2 and 3 in 18 (15%), 79 (61%) and 29 (24%) cases, respectively. Chemotherapy regimens different from FOLFIRINOX and gemcitabine + nab-paclitaxel (OR 11.61 (2.53-53.36), p = 0.002) and lymphovascular invasion (OR 11.28 (1.89-67.23), p = 0.008) were associated to PR-3. Median follow-up was 25.8 (3.6-130.5) months. For PR-0/1, PR-2 and PR-3, median DFS was 45.8, 11.5, 4.6 months (p < 0.0001), respectively, while median OS was not reached, 27.1 and 17.5 months (p = 0.0006), respectively. At univariate analysis, PR-0/1 was significantly associated to better DFS and OS (HR 0.33 (0.17-0.67), p = 0.002; HR 0.20 (0.07-0.54), p = 0.002, respectively). At multivariate analysis, pancreaticoduodenectomy (HR 0.50 (0.30-0.84), p = 0.009), LNR (HR 27.14 (1.21-608.9), p = 0.038) and lymphovascular invasion (HR 1.99 (1.06-3.76), p = 0.033) were independently associated to DFS; pre-treatment CA 19.9 value (HR 1.00 (1.00-1.00), p = 0.025), post-treatment resectability status (HR 0.51 (0.28-0.95), p = 0.035), pancreaticoduodenectomy (HR 0.56 (0.32-0.99), p = 0.050), severe morbidity (2.99 (1.22-7.55), p = 0.017), LNR (HR 56.8 (2.08-1548.3), p = 0.017), lymphovascular invasion (HR 2.18 (1.08-4.37), p = 0.029) were independently associated to OS. PR did not reach statistical significance at multivariate analysis. A favorable PR is observed only in a limited number of cases. The prognostic role of PR, despite being promising, remains unclear and further multicentric studies are needed.
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Affiliation(s)
- G Donisi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - G Nappo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy.
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy.
| | - M Pacilli
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - G L Capretti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - P Spaggiari
- Department of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - M Sollai
- Department of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - S Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
| | - A Zerbi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Milan, Pieve Emanuele, Italy
- Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Milan, Rozzano, Italy
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Song XY, Liu J, Li HX, Cai XW, Li ZG, Su YC, Li Y, Dong XH, Yu W, Fu XL. Enhancing Prediction for Tumor Pathologic Response to Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Cancer by Dynamic Parameters from Clinical Assessments. Cancers (Basel) 2023; 15:4377. [PMID: 37686655 PMCID: PMC10486879 DOI: 10.3390/cancers15174377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/10/2023] Open
Abstract
To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.
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Affiliation(s)
- Xin-Yun Song
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
- School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
| | - Jun Liu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Hong-Xuan Li
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xu-Wei Cai
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Zhi-Gang Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yu-Chen Su
- Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Yue Li
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xiao-Huan Dong
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Wen Yu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
| | - Xiao-Long Fu
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; (X.-Y.S.)
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Wang S, Di S, Lu J, Xie S, Yu Z, Liang Y, Gong T. 18 F-FDG PET/CT predicts the role of neoadjuvant immunochemotherapy in the pathological response of esophageal squamous cell carcinoma. Thorac Cancer 2023; 14:2338-2349. [PMID: 37424279 PMCID: PMC10447171 DOI: 10.1111/1759-7714.15024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 07/11/2023] Open
Abstract
BACKGROUND This study aimed to investigate the predictive value of 18 F-FDG PET/CT for pathological response after neoadjuvant immunochemotherapy (NICT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS The clinical data of 54 patients with ESCC who underwent two cycles of NICT followed by surgery were retrospectively analyzed. NICT consisted of PD-1 blockade therapy combined with chemotherapy. 18 F-FDG PET/CT scans were performed before and after NICT. The pathological results after surgery were used to assess the degree of pathological response. The scan parameters of 18 F-FDG PET/CT and their changes before and after NICT were compared with the pathological response. RESULTS Among the 54 patients, 10 (18.5%) achieved complete pathological response (pCR) and 21 (38.9%) achieved major pathological response (MPR). The post-NICT scan parameters and their changes were significantly associated with the pathological response. In addition, the values of the changes in the scanned parameters before and after treatment can further predict the pathological response of the patient. CONCLUSION 18 F-FDG PET/CT is a useful tool to evaluate the efficacy of NICT and predict pathological response in patients with ESCC. The post-NICT scan parameters and their changes can help identify patients who are likely to achieve pCR or MPR.
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Affiliation(s)
- Shuohua Wang
- Department of Thoracic SurgeryNavy Clinical College, Anhui Medical UniversityHefeiChina
- Department of Thoracic SurgeryThe Fifth School of Clinical Medicine, Anhui Medical UniversityHefeiChina
| | - Shouyin Di
- Department of Thoracic SurgeryThe Sixth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Jing Lu
- Department of Thoracic SurgeryThe Sixth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Shun Xie
- Department of Thoracic SurgeryNavy Clinical College, Anhui Medical UniversityHefeiChina
- Department of Thoracic SurgeryThe Fifth School of Clinical Medicine, Anhui Medical UniversityHefeiChina
| | - Zhenyang Yu
- Department of PathologyThe Sixth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Yingkui Liang
- Department of Nuclear MedicineThe Sixth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Taiqian Gong
- Department of Thoracic SurgeryNavy Clinical College, Anhui Medical UniversityHefeiChina
- Department of Thoracic SurgeryThe Fifth School of Clinical Medicine, Anhui Medical UniversityHefeiChina
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Yang Z, Gong J, Li J, Sun H, Pan Y, Zhao L. The gap before real clinical application of imaging-based machine-learning and radiomic models for chemoradiation outcome prediction in esophageal cancer: a systematic review and meta-analysis. Int J Surg 2023; 109:2451-2466. [PMID: 37463039 PMCID: PMC10442126 DOI: 10.1097/js9.0000000000000441] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 05/01/2023] [Indexed: 08/21/2023]
Abstract
BACKGROUND Due to tumoral heterogeneity and the lack of robust biomarkers, the prediction of chemoradiotherapy response and prognosis in patients with esophageal cancer (EC) is challenging. The goal of this study was to assess the study quality and clinical value of machine learning and radiomic-based quantitative imaging studies for predicting the outcomes of EC patients after chemoradiotherapy. MATERIALS AND METHODS PubMed, Embase, and Cochrane were searched for eligible articles. The methodological quality and risk of bias were evaluated using the Radiomics Quality Score (RQS), Image Biomarkers Standardization Initiative (IBSI) Guideline, and Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement, as well as the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. A meta-analysis of the evidence focusing on predicting chemoradiotherapy response and outcome in EC patients was implemented. RESULTS Forty-six studies were eligible for qualitative synthesis. The mean RQS score was 9.07, with an adherence rate of 42.52%. The adherence rates of the TRIPOD and IBSI were 61.70 and 43.17%, respectively. Ultimately, 24 studies were included in the meta-analysis, of which 16 studies had a pooled sensitivity, specificity, and area under the curve (AUC) of 0.83 (0.76-0.89), 0.83 (0.79-0.86), and 0.84 (0.81-0.87) in neoadjuvant chemoradiotherapy datasets, as well as 0.84 (0.75-0.93), 0.89 (0.83-0.93), and 0.93 (0.90-0.95) in definitive chemoradiotherapy datasets, respectively. Moreover, radiomics could distinguish patients from the low-risk and high-risk groups with different disease-free survival (DFS) (pooled hazard ratio: 3.43, 95% CI 2.39-4.92) and overall survival (pooled hazard ratio: 2.49, 95% CI 1.91-3.25). The results of subgroup and regression analyses showed that some of the heterogeneity was explained by the combination with clinical factors, sample size, and usage of the deep learning (DL) signature. CONCLUSIONS Noninvasive radiomics offers promising potential for optimizing treatment decision-making in EC patients. However, it is necessary to make scientific advancements in EC radiomics regarding reproducibility, clinical usefulness analysis, and open science categories. Improved model reporting of study objectives, blind assessment, and image processing steps are required to help promote real clinical applications of radiomics in EC research.
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Affiliation(s)
- Zhi Yang
- Department of Radiation Oncology, Xijing Hospital
| | - Jie Gong
- Department of Radiation Oncology, Xijing Hospital
| | - Jie Li
- Department of Radiation Oncology, Xijing Hospital
| | - Hongfei Sun
- Department of Radiation Oncology, Xijing Hospital
| | - Yanglin Pan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an, People’s Republic of China
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital
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S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:701-745. [PMID: 37285870 DOI: 10.1055/a-1771-7087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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Kitti PM, Faltinova M, Kauppi J, Räsänen J, Saarto T, Seppälä T, Anttonen AM. Chemoradiation for oesophageal cancer: the choice of treatment modality. Radiat Oncol 2023; 18:93. [PMID: 37259100 DOI: 10.1186/s13014-023-02290-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 05/25/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND Locally advanced oesophageal cancer can be treated with definitive chemoradiation (dCRT) or with neoadjuvant chemoradiation followed by surgery (nCRT + S), but treatment modality choice is not always clear. The aim of this study was to investigate the factors associated with the choice of treatment modality in locally advanced oesophageal cancer. METHODS This was a retrospective cohort study of 149 patients treated with dCRT(n = 85) or nCRT + S (n = 64) for oesophageal cancer in Helsinki University Hospital in 2008-2018. Logistic regression was used to analyse factors associated with choice of treatment modality and to compare dosimetric factors with postoperative complications. Multivariate analyses identified factors associated with survival. RESULTS Surgery was performed after chemoradiation as planned on 64/91 patients (70%). 28/64 had pathological complete response (44%). Probability of nCRT + S was higher in stages I-III versus IV (OR 3.62, 95% CI 1.53-8.53; P = .003), ECOG 0-1 versus 2 (OR 6.99, 95% CI 1.81-26.96; P = .005) or in the middle/lower vs upper oesophageal tumours (OR 5.61, 95% CI 1.83-17.16, P = .003). Probability for surgery was lower, if patient had lost > 10% of body weight (OR 0.46, 95% CI 0.21-0.98, P = 0.043). Patients in the nCRT + S group had significantly better median overall survival (mOS) and local control than the dCRT group (60 vs. 10 months, P < .001 and 53 vs. 6 months, P < 0.0001, respectively). 10/85 (12%) patients died within three months after dCRT. In multivariate analysis, nCRT + S was associated with improved mOS (HR 0.28, 95% CI 0.17-0.44, P < .001). Current smokers had worse mOS (HR 2.02, 95% CI 1.04-3.92, P = .037) compared to never-smokers. No significant dosimetric factor associated with postoperative complications was found. CONCLUSION The overall clinical status of the patients and the stage of the cancer guide the choice of treatment modalities, leading to overtreatment. Patients with better prognoses were more likely operated after chemoradiation, although there is no evidence of OS benefit in previous randomized trials. On the other hand, the prognosis was poor for patients with poor general health and advanced cancers, despite the chemoradiation. Thus, there are signs of overtreatment. MDT practice should be recommended to optimise the choice of treatment modalities. Smoking status is an independent factor associated with survival.
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Affiliation(s)
- Pauliina M Kitti
- Department of Oncology, HUS Comprehensive Cancer Centre and University of Helsinki, Paciuksenkatu 3, PL 180, 00029 HUS, Helsinki, Finland.
| | - Maria Faltinova
- Department of Oncology, HUS Comprehensive Cancer Centre and University of Helsinki, Paciuksenkatu 3, PL 180, 00029 HUS, Helsinki, Finland
| | - Juha Kauppi
- Department of General Thoracic and Esophageal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Jari Räsänen
- Department of General Thoracic and Esophageal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Tiina Saarto
- Department of Oncology, HUS Comprehensive Cancer Centre and University of Helsinki, Paciuksenkatu 3, PL 180, 00029 HUS, Helsinki, Finland
| | - Tiina Seppälä
- Department of Oncology, HUS Comprehensive Cancer Centre and University of Helsinki, Paciuksenkatu 3, PL 180, 00029 HUS, Helsinki, Finland
| | - Anu M Anttonen
- Department of Oncology, HUS Comprehensive Cancer Centre and University of Helsinki, Paciuksenkatu 3, PL 180, 00029 HUS, Helsinki, Finland
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Ren Q, Zhang P, Zhang X, Feng Y, Li L, Lin H, Yu Y. A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer. Front Immunol 2023; 14:1199040. [PMID: 37313409 PMCID: PMC10258351 DOI: 10.3389/fimmu.2023.1199040] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 05/19/2023] [Indexed: 06/15/2023] Open
Abstract
Background Current paradigms of anti-tumor therapies are not qualified to evacuate the malignancy ascribing to cancer stroma's functions in accelerating tumor relapse and therapeutic resistance. Cancer-associated fibroblasts (CAFs) has been identified significantly correlated with tumor progression and therapy resistance. Thus, we aimed to probe into the CAFs characteristics in esophageal squamous cancer (ESCC) and construct a risk signature based on CAFs to predict the prognosis of ESCC patients. Methods The GEO database provided the single-cell RNA sequencing (scRNA-seq) data. The GEO and TCGA databases were used to obtain bulk RNA-seq data and microarray data of ESCC, respectively. CAF clusters were identified from the scRNA-seq data using the Seurat R package. CAF-related prognostic genes were subsequently identified using univariate Cox regression analysis. A risk signature based on CAF-related prognostic genes was constructed using Lasso regression. Then, a nomogram model based on clinicopathological characteristics and the risk signature was developed. Consensus clustering was conducted to explore the heterogeneity of ESCC. Finally, PCR was utilized to validate the functions that hub genes play on ESCC. Results Six CAF clusters were identified in ESCC based on scRNA-seq data, three of which had prognostic associations. A total of 642 genes were found to be significantly correlated with CAF clusters from a pool of 17080 DEGs, and 9 genes were selected to generate a risk signature, which were mainly involved in 10 pathways such as NRF1, MYC, and TGF-Beta. The risk signature was significantly correlated with stromal and immune scores, as well as some immune cells. Multivariate analysis demonstrated that the risk signature was an independent prognostic factor for ESCC, and its potential in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the CAF-based risk signature and clinical stage was developed, which exhibited favorable predictability and reliability for ESCC prognosis prediction. The consensus clustering analysis further confirmed the heterogeneity of ESCC. Conclusion The prognosis of ESCC can be effectively predicted by CAF-based risk signatures, and a comprehensive characterization of the CAF signature of ESCC may aid in interpreting the response of ESCC to immunotherapy and offer new strategies for cancer treatment.
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Affiliation(s)
- Qianhe Ren
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Pengpeng Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanlong Feng
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Long Li
- Department of Thoracic Surgery, Nanjing Gaochun People’s Hospital, Nanjing, China
| | - Haoran Lin
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yue Yu
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Amezcua-Hernandez V, Jimenez-Rosales R, Martinez-Cara JG, Garcia-Garcia J, Valverde Lopez F, Redondo-Cerezo E. Preoperative EUS vs. PET-CT Evaluation of Response to Neoadjuvant Therapy for Esophagogastric Cancer and Its Correlation with Survival. Cancers (Basel) 2023; 15:cancers15112941. [PMID: 37296903 DOI: 10.3390/cancers15112941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 05/22/2023] [Accepted: 05/24/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. METHODS We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3-77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8-81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3-73%). Kaplan-Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. CONCLUSION Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.
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Affiliation(s)
| | - Rita Jimenez-Rosales
- Department of Gastroenterology, "Virgen de las Nieves" University Hospital, 18014 Granada, Spain
| | | | - Javier Garcia-Garcia
- Department of Oncology, "Virgen de las Nieves" University Hospital, 18014 Granada, Spain
| | - Francisco Valverde Lopez
- Department of Gastroenterology, "Virgen de las Nieves" University Hospital, 18014 Granada, Spain
| | - Eduardo Redondo-Cerezo
- Department of Gastroenterology, "Virgen de las Nieves" University Hospital, 18014 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18014 Granada, Spain
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Cheng D, Zhao W, Chen R, Li D, Tang S, Fang C, Ji M. Neoadjuvant PD-1 blockade combined with chemotherapy is not superior to neoadjuvant chemotherapy alone in resectable locally advanced esophageal carcinoma. World J Surg Oncol 2023; 21:33. [PMID: 36737768 PMCID: PMC9896760 DOI: 10.1186/s12957-023-02915-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy followed by surgery has been recommended as standard treatment in patients with locally advanced esophageal cancer (LAEC). But the risk of tumor recurrence still remained, and many patients refused or abandoned radiotherapy because of the intolerable adverse effects in China. Neoadjuvant immunochemotherapy (nICT) followed by surgery has become an emerging treatment in patients with esophageal cancer. There was still no consensus on whether nICT was superior to nCT alone in patients with esophageal cancer. METHODS In this retrospective study, patients with resectable esophageal cancer who received surgery after nICT (n=26, 40%) or nCT alone (n=39, 60%) were included. The patients were classified as nICT or nCT arm. The primary endpoints were pathological tumor response (PTR) and event-free survival (EFS). The different clinic-pathological features were compared by the Kruskal-Wallis test for continuous variables and the Chi-square (χ2) test for categorical variables. Kaplan-Meier curves were used to estimate EFS from the date of treatment to recurrence or death. All tests were 2-sided with a significative P-value defined <.05. RESULTS Three (11.5%) of the 26 patients achieved pathological complete remission (pCR) in the nICT group, and four (10.3%) of the 39 patients achieved pCR in the nCT group, respectively (P=1.000). Six (23.1%) of the 26 patients achieved major pathological response (MPR) in the nICT group, and 11 (28.2%) of the 39 patients achieved MPR in the nCT group, respectively (P=0.645). Downstaging was achieved in 13 (44.8%) patients in the nICT group and 16 (55.2%) patients in the nCT group, respectively (P=0.732). To verify the tumor regression grade (TRG) results, we compared them with MPR and pCR, which showed a significant dependency (P< 0.001). Patients who achieved downgrading showed better MPR and pCR rates (P<0.001 and P =0.010). There was no significant difference in EFS between the nICT and nCT groups (HR=1.011, 95% CI: 0.421-2.425, P = 0.981). CONCLUSIONS Neoadjuvant PD-1 blockade combined with chemotherapy was not superior to chemotherapy alone for patients with resectable locally advanced esophageal carcinoma. However, more studies with long-term follow-up were needed to confirm this result.
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Affiliation(s)
- Daoan Cheng
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China
| | - Weiqing Zhao
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China
| | - Rui Chen
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China
| | - Dong Li
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China
| | - Shuxian Tang
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China
| | - Cheng Fang
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China.
| | - Mei Ji
- Departments of Oncology, the Third Affiliated Hospital of Soochow University, Changzhou, 213004, China.
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Theeuwen H, Atay SM. The role of surveillance and salvage esophagectomy in previously treated esophageal cancer. J Surg Oncol 2023; 127:233-238. [PMID: 36630103 DOI: 10.1002/jso.27182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 01/12/2023]
Abstract
Esophageal cancer remains a significant cause of cancer-related mortality among men and women in the United States. The utility of surgery, as either an immediate or delayed resection in the form of esophagectomy following neoadjuvant therapy in local-regionally advanced esophageal cancer, remains controversial. While neoadjuvant therapy followed by immediate surgery is a guideline-concordant treatment, emerging data suggests that active surveillance with delayed resection at the time of local-regional recurrence may be considered.
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Affiliation(s)
- Hailey Theeuwen
- Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, California, USA
| | - Scott M Atay
- Division of Thoracic Surgery, Department of Surgery, University of Southern California Keck School of Medicine, Los Angeles, California, USA
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Shang QX, Kong WL, Huang WH, Xiao X, Hu WP, Yang YS, Zhang H, Yang L, Yuan Y, Chen LQ. Identification of m6a-related signature genes in esophageal squamous cell carcinoma by machine learning method. Front Genet 2023; 14:1079795. [PMID: 36733344 PMCID: PMC9886874 DOI: 10.3389/fgene.2023.1079795] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/03/2023] [Indexed: 01/19/2023] Open
Abstract
Background: We aimed to construct and validate the esophageal squamous cell carcinoma (ESCC)-related m6A regulators by means of machine leaning. Methods: We used ESCC RNA-seq data of 66 pairs of ESCC from West China Hospital of Sichuan University and the transcriptome data extracted from The Cancer Genome Atlas (TCGA)-ESCA database to find out the ESCC-related m6A regulators, during which, two machine learning approaches: RF (Random Forest) and SVM (Support Vector Machine) were employed to construct the model of ESCC-related m6A regulators. Calibration curves, clinical decision curves, and clinical impact curves (CIC) were used to evaluate the predictive ability and best-effort ability of the model. Finally, western blot and immunohistochemistry staining were used to assess the expression of prognostic ESCC-related m6A regulators. Results: 2 m6A regulators (YTHDF1 and HNRNPC) were found to be significantly increased in ESCC tissues after screening out through RF machine learning methods from our RNA-seq data and TCGA-ESCA database, respectively, and overlapping the results of the two clusters. A prognostic signature, consisting of YTHDF1 and HNRNPC, was constructed based on our RNA-seq data and validated on TCGA-ESCA database, which can serve as an independent prognostic predictor. Experimental validation including the western and immunohistochemistry staining were further successfully confirmed the results of bioinformatics analysis. Conclusion: We constructed prognostic ESCC-related m6A regulators and validated the model in clinical ESCC cohort as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Long-Qi Chen
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Mei PY, Xiao H, Guo Q, Meng WY, Wang ML, Huang QF, Liao YD. Identification and validation of DPY30 as a prognostic biomarker and tumor immune microenvironment infiltration characterization in esophageal cancer. Oncol Lett 2022; 25:68. [PMID: 36644145 PMCID: PMC9827447 DOI: 10.3892/ol.2022.13654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/10/2022] [Indexed: 12/28/2022] Open
Abstract
Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA.
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Affiliation(s)
- Pei-Yuan Mei
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Han Xiao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Qiang Guo
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Wang-Yang Meng
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Ming-Liang Wang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Quan-Fu Huang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China,Correspondence to: Professor Yong-De Liao or Dr Quan-Fu Huang, Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China, E-mail: , E-mail:
| | - Yong-De Liao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China,Correspondence to: Professor Yong-De Liao or Dr Quan-Fu Huang, Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China, E-mail: , E-mail:
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Change in Density Not Size of Esophageal Adenocarcinoma During Neoadjuvant Chemotherapy Is Associated with Improved Survival Outcomes. J Gastrointest Surg 2022; 26:2417-2425. [PMID: 36214951 DOI: 10.1007/s11605-022-05422-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/16/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Changes in the size and density of esophageal malignancy during neoadjuvant chemotherapy (NCT) may be useful in predicting overall survival (OS). The aim of this study was to explore this relationship in patients with adenocarcinoma. METHODS A retrospective single-centre cohort study was performed. Consecutive patients with esophageal adenocarcinoma who received NCT followed by en bloc resection with curative intent were identified. Pre- and post-NCT computed tomography scans were reviewed. The percentage difference between the greatest tumor diameter, esophageal wall thickness and tumor density was calculated. Multivariate Cox regression analysis identified variables independently associated with OS. A ROC analysis was performed on radiological markers to identify optimal cut-off points with Kaplan-Meier plots subsequently created. RESULTS Of the 167 identified, 88 (51.5%) had disease of the gastro-esophageal junction and 149 (89.2%) were clinical T3. In total, 122 (73.1%) had node-positive disease. Increased tumor density (HR 1.01 per % change, 95% CI 1.00-1.02, p = 0.007), lymphovascular invasion (HR 3.23, 95% CI 1.34-7.52, p = 0.006) and perineural invasion (HR 2.51, 95% CI 1.03-6.08, p = 0.048) were independently associated with a decrease in OS. Patients who had a decrease in their tumor density during the time they received NCT of ≥ 20% in Hounsfield units had significantly longer OS than those who did not (75.5 months versus 34.4 months, 95% CI 38.83-105.13/18.63-35.07, p = 0.025). CONCLUSIONS Interval changes in the density, not size, of esophageal adenocarcinoma during the time that NCT are independently associated with OS.
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Jones CM, O'Connor H, O'Donovan M, Hayward D, Blasko A, Harman R, Malhotra S, Debiram-Beecham I, Alias B, Bailey A, Bateman A, Crosby TD, Falk S, Gollins S, Hawkins MA, Kadri S, Levy S, Radhakrishna G, Roy R, Sripadam R, Fitzgerald RC, Mukherjee S. Use of a non-endoscopic immunocytological device (Cytosponge™) for post chemoradiotherapy surveillance in patients with oesophageal cancer in the UK (CYTOFLOC): A multicentre feasibility study. EClinicalMedicine 2022; 53:101664. [PMID: 36187722 PMCID: PMC9519482 DOI: 10.1016/j.eclinm.2022.101664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/30/2022] [Accepted: 08/31/2022] [Indexed: 11/30/2022] Open
Abstract
Background Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding Cancer Research UK, National Institute for Health Research, Medical Research Council.
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Affiliation(s)
- Christopher M. Jones
- Department of Oncology, University of Cambridge, Cambridge, UK
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Heather O'Connor
- Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, University of Oxford, Oxford, UK
| | - Maria O'Donovan
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Daniel Hayward
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | - Adrienn Blasko
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | - Ruth Harman
- Oncology Clinical Trials Office, University of Oxford, Oxford, UK
| | - Shalini Malhotra
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - Bincy Alias
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | - Adam Bailey
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Andrew Bateman
- Southampton University Hospitals NHS Trust, Southampton, UK
| | - Tom D.L. Crosby
- Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, UK
| | - Stephen Falk
- Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Simon Gollins
- North Wales Cancer Treatment Centre, Glan Clwyd Hospital, Denbighshire, UK
| | - Maria A. Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | - Sudarshan Kadri
- Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Stephanie Levy
- Oncology Clinical Trials Office, University of Oxford, Oxford, UK
- Department of Oncology, University of Oxford, Oxford, UK
| | - Ganesh Radhakrishna
- Christie Hospital, The Christie Hospitals NHS Foundation Trust, Manchester, UK
| | - Rajarshi Roy
- Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Raj Sripadam
- The Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
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Wu P, Zhang Z, Yuan Y, Zhang C, Zhang G, Xue L, Yang H, Wang L, Zheng X, Zhang Y, Yuan Y, Lei R, Yang Z, Zheng B, Xue Q, Sun N, He J. A tumor immune microenvironment-related integrated signature can predict the pathological response and prognosis of esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A multicenter study in China. Int J Surg 2022; 107:106960. [PMID: 36257585 DOI: 10.1016/j.ijsu.2022.106960] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 09/25/2022] [Accepted: 10/11/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China. METHODS During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response (<pCR). Subsequently, we constructed a predictive mRNA and lncRNA signature (SERPINE1, LINC00592, and PRKAG2-AS1) using Fisher's linear discriminant analysis (FLDA) with stepwise variant-selection, followed by validation of its predictive ability in both internal and external cohorts. RESULTS Our signature showed great value in predicting the response to nCRT among ESCC samples and acted as an independent predictive indicator, in addition to demonstrating great potential in estimating patient prognosis. Interestingly, we found that patients with a high signature score had lower PD-L1 and IDO1 expression levels but higher CD8+ T cells infiltration, suggesting that PD-L1 and IDO1 are negatively correlated with a high signature score and further associated with pCR and a better prognosis. CONCLUSION The present study identified a promising three-gene-based predictive signature that has powerful clinical implications for the identification of pCR and a good prognosis among patients with ESCC. Further immune-related exploration may provide an opportunity for future therapeutic combination.
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Affiliation(s)
- Peng Wu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China Department of Pathology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China Department of Pathology, Anyang Cancer Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan, 455000, China Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China Department of Radiotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, China Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, China
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Gupta V, Kulanthaivelu R, Metser U, Ortega C, Darling G, Coburn N, Veit-Haibach P. Acceptance and disparities of PET/CT use in patients with esophageal or gastro-esophageal junction cancer: Evaluation of mature registry data. FRONTIERS IN NUCLEAR MEDICINE (LAUSANNE, SWITZERLAND) 2022; 2:917873. [PMID: 39354957 PMCID: PMC11440829 DOI: 10.3389/fnume.2022.917873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/17/2022] [Indexed: 10/03/2024]
Abstract
Background/rationale PET/CT plays a crucial role in esophageal (EC) and gastroesophageal junction cancer (GEJ) diagnosis and management. Despite endorsement in clinical guidelines, variation in acceptance of PET/CT exists. The aim of this study was to assess the early use of PET/CT among EC and GEJ patients in a regionalized setting and identify factors contributing to disparity in access. Materials and methods Retrospective cohort study of adults with EC or GEJ between 2012 and 2014 from the Population Registry of Esophageal and Stomach Tumours of Ontario and Ontario Health (Cancer Care Ontario). Receipt of PET/CT and relevant demographics were collected, and statistical analysis performed. Continuous data were analysed with t-tests and Wilcoxon rank sum test. Categorical data were analysed with chi-square test. Kaplan-Meier methods were used to estimate median survival. Results Fifty-five percent of patients diagnosed with EC or GEJ between 2012 and 2014 received PET/CT (1321/2390). Eighty-four percent of patients underwent surgical resection (729/870), and 80% receiving radical treatment (496/622) underwent PET/CT. The use of PET/CT increased from 2012 to 2014. Male patients received more PET/CT than females (85% vs.78% p < 0.001).Median survival for the overall cohort was 11.1 months, 17.2 vs. 5.2 months among those who did and did not receive PET/CT and 35 vs. 27 months among the surgical cohort (p = 0.16). Conclusions We found that PET/CT use increased from 2012 to 2014 and that the majority of EC/GEJ patients being considered for curative therapy received PET/CT. There were also gender disparities identified. PET/CT appears to confer a potential survival benefit in our study, although our assessment is limited. Our findings may serve as learned lessons for other new imaging modalities, new indications for PET/CT or even for the introduction of new radiopharmaceuticals for PET/CT.
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Affiliation(s)
- Vaibhav Gupta
- Department of Surgery, University Health Network / Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Roshini Kulanthaivelu
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women’s College Hospital, University of Toronto, Toronto, ON, Canada
| | - Ur Metser
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women’s College Hospital, University of Toronto, Toronto, ON, Canada
| | - Claudia Ortega
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women’s College Hospital, University of Toronto, Toronto, ON, Canada
| | - Gail Darling
- Department of Surgery, University Health Network / Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Natalie Coburn
- Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Patrick Veit-Haibach
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women’s College Hospital, University of Toronto, Toronto, ON, Canada
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Yang Z, Wu G, Zhang X, Gao J, Meng C, Liu Y, Wei Q, Sun L, Wei P, Bai Z, Yao H, Zhang Z. Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer. Front Immunol 2022; 13:1001444. [PMID: 36159842 PMCID: PMC9501688 DOI: 10.3389/fimmu.2022.1001444] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Zhigang Bai
- *Correspondence: Zhongtao Zhang, ; Hongwei Yao, ; Zhigang Bai,
| | - Hongwei Yao
- *Correspondence: Zhongtao Zhang, ; Hongwei Yao, ; Zhigang Bai,
| | - Zhongtao Zhang
- *Correspondence: Zhongtao Zhang, ; Hongwei Yao, ; Zhigang Bai,
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Immunohistochemical analyses of paraffin-embedded sections after primary surgery or trimodality treatment in esophageal carcinoma. Clin Transl Radiat Oncol 2022; 36:106-112. [PMID: 35993091 PMCID: PMC9385880 DOI: 10.1016/j.ctro.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 08/01/2022] [Accepted: 08/01/2022] [Indexed: 11/22/2022] Open
Abstract
Changes in the tumor microenvironment of esophageal cancers, both in squamous cell carcinoma and adenocarcinoma, were found when comparing tumor resection specimen having undergone neoadjuvant radiochemotherapy followed by resection or resection only. Selected markers of the tumor microenvironment, i.e., Ki67, p53, CXCR4 and PD1 were found to be downregulated in hypoxic regions compared to normoxic regions. These findings will be correlated with microscopic tumor extension measurements in a subsequent, prospectively included cohort of esophageal cancer patients. Background The microscopic tumor extension before, during or after radiochemotherapy (RCHT) and its correlation with the tumor microenvironment (TME) are presently unknown. This information is, however, crucial in the era of image-guided, adaptive high-precision photon or particle therapy. Materials and methods In this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis. Results In both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1. Conclusion In this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.
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Key Words
- 5-FU, 5-Fluorouracil
- AC, Adenocarcinoma
- AUC, Area under curve
- BSA, Body surface area
- CT, Computed tomography
- CTV, Clinical target volume
- CXCR4, Chemokine receptor type 4
- Esophageal cancer
- FDG, [18F]-fluorodeoxyglucose
- FFPE, Formalin-fixed paraffin-embedded
- GTV, Gross tumor volume
- HIF-1α, Hypoxia-inducible factor 1-alpha
- HNSCC, Head and neck squamous cell carcinoma
- IgG, Immunoglobulin
- Ki67, Tumor proliferation nuclear protein
- MRI, Magnetic resonance imaging
- Microscopic tumor extension
- NRCHT +R, Neoadjuvant radiochemotherapy followed by resection
- PD1, Programmed death 1 receptor
- PET, Positron emission tomography
- PTV, Planning target volume
- R, Resection
- RCHT, Radiochemotherapy
- Radiochemotherapy
- SCC, Squamous cell carcinoma
- TME, Tumor microenvironment
- Tumor microenvironment
- UKD, University Hospital Carl Gustav Carus Dresden
- Whole slide image analysis
- p53, Tumor suppressor protein
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Chen F, Qiu L, Mu Y, Sun S, Yuan Y, Shang P, Ji B, Wang Q. Neoadjuvant chemoradiotherapy with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma. Front Surg 2022; 9:893372. [PMID: 35983558 PMCID: PMC9379096 DOI: 10.3389/fsurg.2022.893372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
Background Neoadjuvant anti-programmed death receptor-1 (PD-1) blockade has been reported to improve the prognosis of locally advanced esophageal squamous cell carcinoma (ESCC). This study was aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemoradiotherapy in locally advanced ESCC. Methods We retrospectively enrolled ESCC patients who received camrelizumab plus chemoradiotherapy as neoadjuvant therapy before surgery from May 2019 to September 2021. Results A total of 38 eligible patients were enrolled. The neoadjuvant treatment was well tolerated with no serious treatment-related adverse events. 36 (94.7%) patients achieved a R0 resection without hospital mortality or any other serious intraoperative complications. The objective response rate (ORR) was 63.2% and the disease control rate (DCR) was 100.0%. The major pathological response (MPR) was 50.0% and the complete pathological response (pCR) was 39.5%. With a median follow-up of 18.5 months, 6 (15.8%) patients had died. The overall survival (OS) and disease-free survival (DFS) at 12 months were 87.6% and 78.7%, respectively. Subgroup analysis demonstrated that patients who got MPR or pCR achieved improved survival, while PD-L1 expression did not reach statistically difference in predicting survival. Conclusions Neoadjuvant camrelizumab plus chemoradiotherapy is safe and efficacious in treating patients with locally advanced ESCC.
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Affiliation(s)
- Fei Chen
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Lingdong Qiu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yushu Mu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Shibin Sun
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Yulong Yuan
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Pan Shang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Bo Ji
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Qifei Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
- Correspondence: Qifei Wang
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