Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights
Background & Aims: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour underlying imaging traits. We developed and validated imaging-based prognostic syst...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923001702 |
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| author | Gu-Wei Ji Qing Xu Chen-Yu Jiao Ming Lu Zheng-Gang Xu Biao Zhang Yue Yang Ke Wang Xiang-Cheng Li Xue-Hao Wang |
| author_facet | Gu-Wei Ji Qing Xu Chen-Yu Jiao Ming Lu Zheng-Gang Xu Biao Zhang Yue Yang Ke Wang Xiang-Cheng Li Xue-Hao Wang |
| author_sort | Gu-Wei Ji |
| collection | DOAJ |
| description | Background & Aims: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour underlying imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of the tumour immune microenvironment (TIME) underpinning patient-specific imaging traits. Methods: Between January 2009 and December 2019, a total of 322 patients who underwent dynamic computed tomography/magnetic resonance imaging and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n = 193) and validation (n = 129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative variables and one integrating preoperative and postoperative variables, were developed using Cox regression analysis. We then prospectively analysed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence. Results: Preoperative and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumour number, radiological/pathological nodal status, pathological necrosis, and three radiological traits (arterial enhancement pattern, tumour boundary, and capsular retraction) demonstrated good performance in predicting disease-specific (C-statistic >0.80) and disease-free (C-statistic >0.75) survival that outperformed rival models and staging systems across study cohorts (P <0.05 for all). Patients with MICC-RACS score of 0–2 (low risk), 3–5 (medium risk), and ≥6 (high risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive regulatory T cells and M2-like macrophages at the invasive margin were noted in tumours with distinct boundary and capsular retraction, respectively. Conclusions: Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach. Impact and Implications: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumour boundary, and capsular retraction) were highly correlated with heterogeneous tumour-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease. |
| first_indexed | 2024-03-12T13:50:54Z |
| format | Article |
| id | doaj.art-4f497082c5db4ae5baf94e1cc0a71fcc |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-12T13:50:54Z |
| publishDate | 2023-10-01 |
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| series | JHEP Reports |
| spelling | doaj.art-4f497082c5db4ae5baf94e1cc0a71fcc2023-08-23T04:34:08ZengElsevierJHEP Reports2589-55592023-10-01510100839Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insightsGu-Wei Ji0Qing Xu1Chen-Yu Jiao2Ming Lu3Zheng-Gang Xu4Biao Zhang5Yue Yang6Ke Wang7Xiang-Cheng Li8Xue-Hao Wang9Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR ChinaDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Corresponding authors. Address: Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel: +86-13305178713; Fax: +86-68136450 (X.H. Wang); Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-18951999088; Fax: +86-68136450 (X.C. Li); Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-13776683209; Fax: +86-68136450 (Q. Xu).Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR ChinaDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR ChinaDepartment of General Surgery, Yancheng No.1 People’s Hospital, Yancheng, PR ChinaDepartment of General Surgery, The First People’s Hospital of Changzhou, Changzhou, PR ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR China; Corresponding authors. Address: Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel: +86-13305178713; Fax: +86-68136450 (X.H. Wang); Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-18951999088; Fax: +86-68136450 (X.C. Li); Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-13776683209; Fax: +86-68136450 (Q. Xu).Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, PR China; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, PR China; Corresponding authors. Address: Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel: +86-13305178713; Fax: +86-68136450 (X.H. Wang); Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-18951999088; Fax: +86-68136450 (X.C. Li); Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, PR China. Tel.: +86-13776683209; Fax: +86-68136450 (Q. Xu).Background & Aims: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour underlying imaging traits. We developed and validated imaging-based prognostic systems for resected MICCs with an appraisal of the tumour immune microenvironment (TIME) underpinning patient-specific imaging traits. Methods: Between January 2009 and December 2019, a total of 322 patients who underwent dynamic computed tomography/magnetic resonance imaging and curative-intent resection for MICC at three hepatobiliary institutions were retrospectively recruited, divided into training (n = 193) and validation (n = 129) datasets. Two radiological and clinical scoring (RACS) systems, one integrating preoperative variables and one integrating preoperative and postoperative variables, were developed using Cox regression analysis. We then prospectively analysed the TIME of tissue samples from 20 patients who met study criteria from January 2021 to December 2021 using multiplexed immunofluorescence. Results: Preoperative and postoperative MICC-RACS systems built on carbohydrate antigen 19-9, albumin, tumour number, radiological/pathological nodal status, pathological necrosis, and three radiological traits (arterial enhancement pattern, tumour boundary, and capsular retraction) demonstrated good performance in predicting disease-specific (C-statistic >0.80) and disease-free (C-statistic >0.75) survival that outperformed rival models and staging systems across study cohorts (P <0.05 for all). Patients with MICC-RACS score of 0–2 (low risk), 3–5 (medium risk), and ≥6 (high risk) had incrementally worse prognosis after surgery. Significant differences in spatial distribution and infiltration level of immune cells were identified between arterial enhancement patterns. Enhanced infiltration of immunosuppressive regulatory T cells and M2-like macrophages at the invasive margin were noted in tumours with distinct boundary and capsular retraction, respectively. Conclusions: Our MICC-RACS systems are simple but powerful prognostic tools that may facilitate the understanding of spatially distinct TIMEs and patient-tailored immunotherapy approach. Impact and Implications: The progress toward clinical translation of imaging biomarkers for mass-forming intrahepatic cholangiocarcinoma (MICC) is slower than anticipated. Questions remain on the biologic behaviour of MICC underlying imaging traits. In this study, we proposed novel and easy-to-use tools, built on radiological and clinical features, that demonstrated good performance in predicting the prognosis either before or after surgery and outperformed rival models/systems across major imaging modalities. The characteristic radiological traits integrated into prognostic systems (arterial enhancement pattern, tumour boundary, and capsular retraction) were highly correlated with heterogeneous tumour-immune microenvironments, thereby renovating treatment paradigms for this difficult-to-treat disease.http://www.sciencedirect.com/science/article/pii/S2589555923001702Intrahepatic cholangiocarcinomaRadiological traitsCancer prognosisPrediction modelTumour immune microenvironment |
| spellingShingle | Gu-Wei Ji Qing Xu Chen-Yu Jiao Ming Lu Zheng-Gang Xu Biao Zhang Yue Yang Ke Wang Xiang-Cheng Li Xue-Hao Wang Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights JHEP Reports Intrahepatic cholangiocarcinoma Radiological traits Cancer prognosis Prediction model Tumour immune microenvironment |
| title | Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights |
| title_full | Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights |
| title_fullStr | Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights |
| title_full_unstemmed | Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights |
| title_short | Translating imaging traits of mass-forming intrahepatic cholangiocarcinoma into the clinic: From prognostic to therapeutic insights |
| title_sort | translating imaging traits of mass forming intrahepatic cholangiocarcinoma into the clinic from prognostic to therapeutic insights |
| topic | Intrahepatic cholangiocarcinoma Radiological traits Cancer prognosis Prediction model Tumour immune microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923001702 |
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