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Mouhanna P, Ståhlberg A, Andersson D, Albu‐Kareem A, Elinder E, Eriksson O, Kavanagh A, Kovács A, Larsson KF, Linderholm B, Uminska M, Österlund T, Howell SJ, Ekholm M. Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements. Int J Cancer 2025; 156:1509-1517. [PMID: 39692755 PMCID: PMC11826139 DOI: 10.1002/ijc.35292] [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: 10/09/2024] [Revised: 11/21/2024] [Accepted: 11/28/2024] [Indexed: 12/19/2024]
Abstract
Circulating tumour DNA (ctDNA) is an emerging biomarker for monitoring cancers. The personalised disease monitoring in metastatic breast cancer (PDM-MBC) study is an ongoing study instigated to evaluate ctDNA as a biomarker to individualise imaging requirements in patients with MBC. Patients receiving first-line endocrine therapy (aromatase inhibitor + cyclin-dependent kinase 4/6 inhibitor) had plasma samples collected pre-treatment, weeks 2 and 4, and concurrently with imaging until progressive disease (PD). Here, we apply an experimental analytical workflow for ultrasensitive ctDNA analysis, utilising personalised ctDNA panels designed from mutations identified in tumour tissue, and present results for 24 patients. Twenty patients (83%) had detectable ctDNA pre-treatment. The median progression-free survival was 25.6 months, and 13 patients experienced PD, with rising ctDNA detected at or prior to PD in 12 patients (92%). If imaging had been omitted until the detection of rising ctDNA for at least one mutation, 68% (n = 71) of the scans performed amongst ctDNA-positive patients would have been avoided. Our results demonstrate that integration of personalised ctDNA monitoring of patients with MBC has potential to substantially reduce the imaging needs in patients showing ctDNA response to treatment.
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Affiliation(s)
- Pia Mouhanna
- Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of OncologyRyhov County HospitalJönköpingSweden
| | - Anders Ståhlberg
- Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Clinical Genetics and GenomicsSahlgrenska University HospitalGothenburgSweden
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
| | - Daniel Andersson
- Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | | | | | - Olle Eriksson
- Futurum – The Academy for Health and CareJönköping CountySweden
| | - Amy Kavanagh
- Department of Medical OncologyThe Christie NHS Foundation TrustManchesterUK
| | - Anikó Kovács
- Department of Clinical PathologySahlgrenska University HospitalGothenburgSweden
| | - Karolina F. Larsson
- Sahlgrenska Center for Cancer Research, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of OncologySahlgrenska University HospitalGothenburgSweden
| | - Barbro Linderholm
- Sahlgrenska Center for Cancer Research, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of OncologySahlgrenska University HospitalGothenburgSweden
| | - Monika Uminska
- Department of OncologyKalmar County HospitalKalmarSweden
| | - Tobias Österlund
- Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of Clinical Genetics and GenomicsSahlgrenska University HospitalGothenburgSweden
- Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
| | - Sacha J. Howell
- Department of Medical OncologyThe Christie NHS Foundation TrustManchesterUK
- Division of Cancer Sciences, Faculty of Biology, Medicine and HealthThe University of ManchesterManchesterUK
| | - Maria Ekholm
- Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Department of OncologyRyhov County HospitalJönköpingSweden
- Department of Biomedical and Clinical Sciences, Division of OncologyLinköping UniversityLinköpingSweden
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Crimì F, Turatto F, D'Alessandro C, Sussan G, Iacobone M, Torresan F, Tizianel I, Campi C, Quaia E, Caccese M, Ceccato F. Texture analysis can predict response to etoposide-doxorubicin-cisplatin in patients with adrenocortical carcinoma. J Endocrinol Invest 2025; 48:711-720. [PMID: 39382628 PMCID: PMC11876227 DOI: 10.1007/s40618-024-02476-2] [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: 07/10/2024] [Accepted: 10/04/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs. METHODS We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups. RESULTS Long-run high grey level emphasis (LRHGLE_GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment. CONCLUSIONS Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC.
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Affiliation(s)
- Filippo Crimì
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Institute of Radiology, University-Hospital of Padova, Padova, Italy
| | - Francesca Turatto
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Institute of Radiology, University-Hospital of Padova, Padova, Italy
| | - Carlo D'Alessandro
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Institute of Radiology, University-Hospital of Padova, Padova, Italy
| | - Giovanni Sussan
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Institute of Radiology, University-Hospital of Padova, Padova, Italy
| | - Maurizio Iacobone
- Endocrine Surgery Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, 35128, Italy
| | - Francesca Torresan
- Endocrine Surgery Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, 35128, Italy
| | - Irene Tizianel
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Endocrinology Unit, Department of Medicine-DIMED, University of Padova, Via Ospedale Civile, Padova, 105 - 35128, Italy
| | - Cristina Campi
- Department of Mathematics, University of Genoa, Genoa, Italy
- Life Science Computational Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genoa, Italy
| | - Emilio Quaia
- Department of Medicine-DIMED, University of Padova, Padova, Italy
- Institute of Radiology, University-Hospital of Padova, Padova, Italy
| | - Mario Caccese
- Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Filippo Ceccato
- Department of Medicine-DIMED, University of Padova, Padova, Italy.
- Endocrinology Unit, Department of Medicine-DIMED, University of Padova, Via Ospedale Civile, Padova, 105 - 35128, Italy.
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He Z, Sa R, Zhang K, Wang J, Qiu X, Chen L. Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan. Clin Radiol 2024; 79:e949-e956. [PMID: 38641445 DOI: 10.1016/j.crad.2024.03.013] [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: 11/09/2023] [Revised: 02/27/2024] [Accepted: 03/25/2024] [Indexed: 04/21/2024]
Abstract
AIM As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. RESULTS A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa = 0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. CONCLUSION This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.
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Affiliation(s)
- Z He
- Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600(#) Yishan Rd, Shanghai 200233, People's Republic of China.
| | - R Sa
- Department of Nuclear Medicine, The First Hospital of Jilin University, 1(#) Xinmin St, Changchun 130021, People's Republic of China.
| | - K Zhang
- Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600(#) Yishan Rd, Shanghai 200233, People's Republic of China.
| | - J Wang
- Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600(#) Yishan Rd, Shanghai 200233, People's Republic of China.
| | - X Qiu
- Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600(#) Yishan Rd, Shanghai 200233, People's Republic of China.
| | - L Chen
- Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600(#) Yishan Rd, Shanghai 200233, People's Republic of China.
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Liu Y, Huang J, Chen JC, Chen W, Pan Y, Qiu J. Predicting treatment response in multicenter non-small cell lung cancer patients based on federated learning. BMC Cancer 2024; 24:688. [PMID: 38840081 PMCID: PMC11155008 DOI: 10.1186/s12885-024-12456-7] [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: 04/24/2024] [Accepted: 05/30/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Multicenter non-small cell lung cancer (NSCLC) patient data is information-rich. However, its direct integration becomes exceptionally challenging due to constraints involving different healthcare organizations and regulations. Traditional centralized machine learning methods require centralizing these sensitive medical data for training, posing risks of patient privacy leakage and data security issues. In this context, federated learning (FL) has attracted much attention as a distributed machine learning framework. It effectively addresses this contradiction by preserving data locally, conducting local model training, and aggregating model parameters. This approach enables the utilization of multicenter data with maximum benefit while ensuring privacy safeguards. Based on pre-radiotherapy planning target volume images of NSCLC patients, a multicenter treatment response prediction model is designed by FL for predicting the probability of remission of NSCLC patients. This approach ensures medical data privacy, high prediction accuracy and computing efficiency, offering valuable insights for clinical decision-making. METHODS We retrospectively collected CT images from 245 NSCLC patients undergoing chemotherapy and radiotherapy (CRT) in four Chinese hospitals. In a simulation environment, we compared the performance of the centralized deep learning (DL) model with that of the FL model using data from two sites. Additionally, due to the unavailability of data from one hospital, we established a real-world FL model using data from three sites. Assessments were conducted using measures such as accuracy, receiver operating characteristic curve, and confusion matrices. RESULTS The model's prediction performance obtained using FL methods outperforms that of traditional centralized learning methods. In the comparative experiment, the DL model achieves an AUC of 0.718/0.695, while the FL model demonstrates an AUC of 0.725/0.689, with real-world FL model achieving an AUC of 0.698/0.672. CONCLUSIONS We demonstrate that the performance of a FL predictive model, developed by combining convolutional neural networks (CNNs) with data from multiple medical centers, is comparable to that of a traditional DL model obtained through centralized training. It can efficiently predict CRT treatment response in NSCLC patients while preserving privacy.
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Affiliation(s)
- Yuan Liu
- School of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China
| | - Jinzao Huang
- Department of Radiology, Cathay General Hospital, Taipei, China
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao- Tung University, Taipei, China
| | - Jyh-Cheng Chen
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao- Tung University, Taipei, China
- Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, China
| | - Wei Chen
- School of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China
| | - Yuteng Pan
- School of Radiology, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China
| | - Jianfeng Qiu
- School of Radiology, Second Affiliated Hospital of Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, China.
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Ahn HM, Park I, Kim CG, Ko YK, Gim JA. Factors related to tumor response rate from TCGA three omics data-variants, expression, methylation. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, TOXICOLOGY AND CARCINOGENESIS 2024; 42:173-188. [PMID: 38409772 DOI: 10.1080/26896583.2024.2319010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
The Cancer Genome Atlas (TCGA) and its patient-derived multi-omics datasets have been the backbone of cancer research, and with novel approaches, it continues to shed new insight into the disease. In this study, we delved into a method of multi-omics integration of patient datasets and the association of biological pathways related to the disease. First, across thirty-three types of cancer present in TCGA, we merged genomic mutations and drug response datasets and filtered for the viable variant-drug response combinations available in TCGA, containing more than three samples for each drug response label with RNA sequencing (RNA-seq) and genomic methylation data available for each patient. We identified two distinct combinations in TCGA, one being pancreatic adenocarcinoma patients with/without rs121913529 variant in KRAS gene treated with gemcitabine, and the other low-grade glioma with/without rs121913500 variant in IDH1 gene administered with temozolomide. In these two groups, different patterns of gene expression were observed in the pathways often associated with cancer progression, such as mTOR and PDGF between the patients with complete response and progressive disease. Our result will provide yet another example of the relevance of these biological pathways in cancer drug response and a way for multi-omics integration in cancer datasets.
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Affiliation(s)
- Hyung-Min Ahn
- Center for Lung Cancer, National Cancer Center Hospital, Goyang, South Korea
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea
| | - Insu Park
- BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea
- Department of Laboratory Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Chang Geun Kim
- Center for Lung Cancer, National Cancer Center Hospital, Goyang, South Korea
- Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, Seoul, South Korea
| | - Young Kyung Ko
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Jeong-An Gim
- Department of Medical Science, Soonchunhyang University, Asan, South Korea
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Ha S, Kim YI, Oh JS, Yoo C, Ryoo BY, Ryu JS. Prediction of [ 177Lu]Lu-DOTA-TATE therapy response using the absorbed dose estimated from [ 177Lu]Lu-DOTA-TATE SPECT/CT in patients with metastatic neuroendocrine tumour. EJNMMI Phys 2024; 11:14. [PMID: 38315270 PMCID: PMC10844176 DOI: 10.1186/s40658-024-00620-8] [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: 07/25/2023] [Accepted: 01/29/2024] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [177Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response. METHOD A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1-3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [177Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4-5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses. RESULTS Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299-0.301, p = 0.025-0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198-0.206, p = 0.131-0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209-0.217, p = 0.112-0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031-1.051, p = 0.024-0.026). CONCLUSIONS The cumulative TAD estimated from [177Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [177Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy.
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Affiliation(s)
- Sejin Ha
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong-Il Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- Theranostics Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea.
| | - Jungsu S Oh
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Theranostics Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea
| | - Changhoon Yoo
- Theranostics Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Theranostics Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin-Sook Ryu
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Theranostics Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea
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López-González E, Rodriguez-Jiménez A, Gómez-Salgado J, Daza-Manzano C, Rojas-Luna JA, Alvarez RM. Role of tumor volume in endometrial cancer: An imaging analysis and prognosis significance. Int J Gynaecol Obstet 2023; 163:840-846. [PMID: 37350418 DOI: 10.1002/ijgo.14954] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 06/04/2023] [Indexed: 06/24/2023]
Abstract
OBJECTIVE To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. METHODS A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. RESULTS A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high-grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease-free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005-1.032) and survival (OR 1.027, 95% CI 1.009-1.046). CONCLUSIONS This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC.
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Affiliation(s)
- Elga López-González
- Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain
| | | | - Juan Gómez-Salgado
- Department of Sociology, Social Work and Public Health, Faculty of Labor Sciences, University of Huelva, Huelva, Spain
- Safety and Health Postgraduate Programme, Universidad Espíritu Santo, Guayaquil, Ecuador
| | - Cinta Daza-Manzano
- Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain
| | - José Antonio Rojas-Luna
- Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain
| | - Rosa María Alvarez
- Gynecological Oncology and Breast Cancer Unit, Department of Obstetrics and Gynecology, Hospital Universitario Santa Cristina, Madrid, Spain
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Chen Y, Sa R, Qiu X, Chen L. Second radioiodine treatment hardly benefits TT-DTC patients with radioiodine-negative metastases on initial post-therapeutic whole-body scans. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2023; 67:294-303. [PMID: 37526527 DOI: 10.23736/s1824-4785.23.03518-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
BACKGROUND The effect of second 131I treatment (RT) in totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with true-positive thyroid beds and false-negative metastasis (TB+/M-) on initial post-therapeutic whole-body scan (Rx-WBS) remains unknown. METHODS TT-DTC patients with TB+/M- on initial Rx-WBS receiving and not receiving second RT were categorized into group A and group B, respectively, while patients with 131I-avid metastasis receiving second RT were referred to as group C. Biochemical remission (BR) was defined as a decrease of ≥25.0% in thyrotropin-suppressed thyroglobulin (Tgon) level, while the structural response (SR) was determined by the change in the size of the largest lesion. RESULTS In total, 145 patients were eligible. In group A, the median Tgon measured 3.3 ng/mL before and 3.0 ng/mL at 4 months after second RT (P=0.307), yielding a decrease in the median Tgon (∆Tgon%) of 13.3%, a BR rate of 36%, and an insignificant SR, which were comparable to those in group B. In group C, however, a median ∆Tgon% of 37.8% and a BR rate of 64% were obtained, which were significantly higher than those in group A (P=0.038 and 0.022, respectively), with SR distributions similar to those in group A. In addition, 131I uptake in the neck was not statistically associated with the detection of metastasis on initial Rx-WBS. CONCLUSIONS This controlled study demonstrated a subtle response to second RT in TT-DTC patients with TB+/M- on initial Rx-WBS, representing a meaningful advancement in avoiding ineffective repeated RT.
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Affiliation(s)
- Yun Chen
- Department of Nuclear Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Ri Sa
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
- Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, China
| | - Xian Qiu
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Libo Chen
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China -
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Lother D, Robert M, Elwood E, Smith S, Tunariu N, Johnston SRD, Parton M, Bhaludin B, Millard T, Downey K, Sharma B. Imaging in metastatic breast cancer, CT, PET/CT, MRI, WB-DWI, CCA: review and new perspectives. Cancer Imaging 2023; 23:53. [PMID: 37254225 DOI: 10.1186/s40644-023-00557-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 04/17/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND Breast cancer is the most frequent cancer in women and remains the second leading cause of death in Western countries. It represents a heterogeneous group of diseases with diverse tumoral behaviour, treatment responsiveness and prognosis. While major progress in diagnosis and treatment has resulted in a decline in breast cancer-related mortality, some patients will relapse and prognosis in this cohort of patients remains poor. Treatment is determined according to tumor subtype; primarily hormone receptor status and HER2 expression. Menopausal status and site of disease relapse are also important considerations in treatment protocols. MAIN BODY Staging and repeated evaluation of patients with metastatic breast cancer are central to the accurate assessment of disease extent at diagnosis and during treatment; guiding ongoing clinical management. Advances have been made in the diagnostic and therapeutic fields, particularly with new targeted therapies. In parallel, oncological imaging has evolved exponentially with the development of functional and anatomical imaging techniques. Consistent, reproducible and validated methods of assessing response to therapy is critical in effectively managing patients with metastatic breast cancer. CONCLUSION Major progress has been made in oncological imaging over the last few decades. Accurate disease assessment at diagnosis and during treatment is important in the management of metastatic breast cancer. CT (and BS if appropriate) is generally widely available, relatively cheap and sufficient in many cases. However, several additional imaging modalities are emerging and can be used as adjuncts, particularly in pregnancy or other diagnostically challenging cases. Nevertheless, no single imaging technique is without limitation. The authors have evaluated the vast array of imaging techniques - individual, combined parametric and multimodal - that are available or that are emerging in the management of metastatic breast cancer. This includes WB DW-MRI, CCA, novel PET breast cancer-epitope specific radiotracers and radiogenomics.
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Affiliation(s)
| | - Marie Robert
- Institut de Cancérologie de l'Ouest, St Herblain, France
| | | | - Sam Smith
- The Royal Marsden Hospital, London & Sutton, UK
| | - Nina Tunariu
- The Royal Marsden Hospital, London & Sutton, UK
- The Institute of Cancer Research (ICR), London & Sutton, UK
| | - Stephen R D Johnston
- The Royal Marsden Hospital, London & Sutton, UK
- The Institute of Cancer Research (ICR), London & Sutton, UK
| | | | | | | | - Kate Downey
- The Royal Marsden Hospital, London & Sutton, UK
- The Institute of Cancer Research (ICR), London & Sutton, UK
| | - Bhupinder Sharma
- The Royal Marsden Hospital, London & Sutton, UK.
- The Institute of Cancer Research (ICR), London & Sutton, UK.
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10
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Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors. Cancer Immunol Immunother 2022; 71:2609-2618. [DOI: 10.1007/s00262-022-03180-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 02/16/2022] [Indexed: 10/18/2022]
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11
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Harel R, Kaisman-Elbaz T, Emch T, Elson P, Chao ST, Suh JH, Angelov L. A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology. Neurosurg Focus 2022; 53:E10. [DOI: 10.3171/2022.8.focus22363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/03/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE
Stereotactic body radiotherapy (SBRT) is a precise and conformal treatment modality used in the management of metastatic spine tumors. Multiple studies have demonstrated its safety and efficacy for pain and tumor control. However, no uniform quantitative imaging methodology exists to evaluate response to treatment in these patients. This study presents radiographic local control rates post-SBRT, systematically compares measurements acquired according to WHO and Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and explores the relationship to patient outcome.
METHODS
The authors performed a retrospective review of prospectively obtained data from a cohort of 59 consecutive patients (81 metastatic isocenters) treated with SBRT and followed with serial MRI scans. Measurements were performed by a neuroradiologist blinded to the patients’ clinical course. Local control status was determined according to both WHO and RECIST measurements, and agreement between the measuring methodologies was calculated and reported.
RESULTS
Eighty-one isocenters (111 vertebral bodies) were treated with SBRT. The mean treatment dose was 13.96 Gy and the median follow-up duration was 10.8 months, during which 408 MRI scans were evaluated with both WHO and RECIST criteria for each scan point. Imaging demonstrated a mean unidimensional size decrease of 0.2 cm (p = 0.14) and a mean area size decrease of 0.99 cm2 (p = 0.03). Although 88% of the case classifications were concordant and the agreement was significant, WHO criteria were found to be more sensitive to tumor size change. The local control rates according to WHO and RECIST were 95% and 98%, respectively.
CONCLUSIONS
Although WHO volumetric measurements are admittedly superior for tumor size measurement, RECIST is simpler, reproducible, and for the first time is shown here to be comparable to WHO criteria. Thus, the application of RECIST methodology appears to be a suitable standard for evaluating post-SBRT treatment response. Moreover, using comprehensive and consistent measuring approaches, this study substantiates the efficacy of SBRT in the treatment of spine metastases.
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Affiliation(s)
- Ran Harel
- Department of Neurosurgery, Sheba Medical Center Affiliated to Tel-Aviv University, Tel-Aviv, Israel
| | - Tehila Kaisman-Elbaz
- Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland
- Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland
| | - Todd Emch
- Imaging Institute, Cleveland Clinic, Cleveland
| | - Paul Elson
- Quantitative Health Sciences, Cleveland Clinic, Cleveland; and
| | - Samuel T Chao
- Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - John H Suh
- Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
| | - Lilyana Angelov
- Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland
- Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland
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12
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Wang B, Fan Y, Zhang L, Liu L, Ma Y, Ma X, Huang Y, Wu Y, Liang Y, Xu Y, Wu X. Evaluation of Pembrolizumab Monotherapy Efficacy in Advanced Non-Small-Cell Lung Cancer by Serial Monitoring of Circulating Tumor DNA Using Next-Generation Sequencing. CLINICAL MEDICINE INSIGHTS: ONCOLOGY 2022; 16:11795549221075326. [PMID: 35197718 PMCID: PMC8859670 DOI: 10.1177/11795549221075326] [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: 12/08/2021] [Accepted: 01/04/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Pembrolizumab is widely used in advanced non-small-cell lung cancer (NSCLC) patients with positive programmed death-ligand 1 (PD-L1). However, efficacy evaluation along treatment by serial monitoring of circulating tumor DNA (ctDNA) using next-generation sequencing remained to be well studied. METHODS Nine PD-L1 positive advanced NSCLC patients were prospectively enrolled and received pembrolizumab monotherapy. Pretreatment tissue and/or plasma samples were collected as baseline reference. Serial plasma samples were collected after 3 and 6 weeks of treatment as well as at disease progression. All samples underwent targeted next-generation sequencing. RESULTS The median progression-free survival (mPFS) and median overall survival (mOS) were 4.43 and 25.53 months, respectively. In total, 3 patients achieved partial response (PR) or stable disease (SD) for more than 6 months and were thus classified into the durable clinical benefit (DCB) group, whereas the rest 6 were grouped as nondurable benefit (NDB) patients. Molecular profiling of baseline samples revealed that TP53 and APC were the 2 most frequently mutated genes in all patients, whereas POT1 and SETD2 mutations were enriched in DCB and NDB groups, respectively. Higher tumor mutational burden (TMB) was observed in DCB patients than NDB group. During serial ctDNA monitoring, 2 DCB patients showed a dramatic ctDNA reduction while 75% of NDB patients' ctDNA concentration increased at week 6. Several acquired mutations might contribute to the pembrolizumab resistance, including CDKN2A frameshift and MITF nonsense mutations. CONCLUSIONS Genomic profiling of peripheral blood samples can be applied to dynamically monitor disease progression. The reduction in ctDNA concentration during treatment implied DCBs.
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Affiliation(s)
- Buhai Wang
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Yaqin Fan
- Department of Medical Oncology, Jiaxing First Hospital, Jiaxing, China
| | - Liying Zhang
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Liqin Liu
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Yutong Ma
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Xiaosong Ma
- Department of Oncology, Dalian Medical University, Dalian, China
| | - Yuxiang Huang
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Yinxia Wu
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Yichen Liang
- Cancer Institute, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Yang Xu
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Xue Wu
- Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China
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Interstitial Control-Released Polymer Carrying a Targeting Small-Molecule Drug Reduces PD-L1 and MGMT Expression in Recurrent High-Grade Gliomas with TMZ Resistance. Cancers (Basel) 2022; 14:cancers14041051. [PMID: 35205800 PMCID: PMC8870243 DOI: 10.3390/cancers14041051] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/08/2022] [Accepted: 02/13/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary This study reports a potential new drug—Cerebraca wafer—that is designed to deliver its active pharmaceutical ingredient, (Z)-n-butylidenephthalide (BP), directly into the surgical cavity created when a brain tumor is resected. The therapeutic mechanism of Cerebraca wafer was shown to involve the following: (1) an IC50 of BP against tumor stem cells four times lower than that of bis-chloroethylnitrosourea (BCNU); (2) a synergistic effect between BP and temozolomide (TMZ), as demonstrated by a reduction in O6-methylguanine-DNA-methyltransferase (MGMT) expression level; (3) BP inhibition of programmed cell death-ligand 1 (PD-L1) protein levels, thereby activating T-cell cytotoxicity and increasing interferon-gamma (IFN-γ) secretion. The implantation of Cerebraca wafer is safe, no drug-related adverse events (AEs) and serious AEs (SAEs) were found. The median overall survival (OS) of patients receiving high-dose Cerebraca wafer have exceeded 17.4 months, and a 100% progression-free survival (PFS) rate at six month was achieved. In sum, these findings demonstrate that the Cerebraca wafer has superior therapeutic effects to Gliadel wafer in recurrent high-grade gliomas. Abstract In recurrent glioblastoma, Gliadel wafer implantation after surgery has been shown to result in incomplete chemical removal of residual tumor and development of brain edema. Furthermore, temozolomide (TMZ) resistance caused by O6-methylguanine-DNA-methyltransferase (MGMT) activation and programmed cell death-ligand 1 (PD-L1) expression leads to immune-cold lesions that result in poorer prognosis. Cerebraca wafer, a biodegradable polymer containing (Z)-n-butylidenephthalide (BP), is designed to eliminate residual tumor after glioma resection. An open-label, one-arm study with four dose cohorts, involving a traditional 3 + 3 dose escalation clinical trial, of the Cerebraca wafer combined with TMZ on patients with recurrent high-grade glioma, was conducted. Of the 12 patients who receive implantation of Cerebraca wafer, there were no drug-related adverse events (AEs) or serious AEs (SAEs). The median overall survival (OS) of patients receiving low-dose Cerebraca wafer was 12 months in the group with >25% wafer coverage of the resected tumor, which is longer than OS duration in previously published studies (Gliadel wafer, 6.4 months). Patients who received high-dose Cerebraca wafer treatment had not yet died at the data cut-off date; a 100% progression-free survival (PFS) rate at six month was achieved, indicating the median OS of cohort IV was more than 17.4 months. In vitro study of the primary cells collected from the patients revealed that the IC50 of BP against tumor stem cells was four times lower than that of bis-chloroethylnitrosourea (BCNU). A synergistic effect between BP and TMZ was demonstrated by a reduction in MGMT expression. Furthermore, BP inhibited PD-L1 expression, thereby activating T-cell cytotoxicity and increasing interferon-gamma (IFN-γ) secretion. The better therapeutic effect of Cerebraca wafer on recurrent high-grade glioma could occur through re-sensitization of TMZ and reduction of PD-L1.
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Di Capua D, Bracken-Clarke D, Ronan K, Baird AM, Finn S. The Liquid Biopsy for Lung Cancer: State of the Art, Limitations and Future Developments. Cancers (Basel) 2021; 13:cancers13163923. [PMID: 34439082 PMCID: PMC8391249 DOI: 10.3390/cancers13163923] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/28/2021] [Accepted: 07/29/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary During the development and progression of lung tumors, processes such as necrosis and vascular invasion shed tumor cells or cellular components into various fluid compartments. Liquid biopsies consist of obtaining a bodily fluid, typically peripheral blood, in order to isolate and investigate these shed tumor constituents. Circulating tumor cells (CTCs) are one such constituent, which can be isolated from blood and can act as a diagnostic aid and provide valuable prognostic information. Liquid-based biopsies may also have a potential future role in lung cancer screening. Circulating tumor DNA (ctDNA) is found in small quantities in blood and, with the recent development of sensitive molecular and sequencing technologies, can be used to directly detect actionable genetic alterations or monitor for resistance mutations and guide clinical management. While potential benefits of liquid biopsies are promising, they are not without limitations. In this review, we summarize the current state and limitations of CTCs and ctDNA and possible future directions. Abstract Lung cancer is a leading cause of cancer-related deaths, contributing to 18.4% of cancer deaths globally. Treatment of non-small cell lung carcinoma has seen rapid progression with targeted therapies tailored to specific genetic drivers. However, identifying genetic alterations can be difficult due to lack of tissue, inaccessible tumors and the risk of complications for the patient with serial tissue sampling. The liquid biopsy provides a minimally invasive method which can obtain circulating biomarkers shed from the tumor and could be a safer alternative to tissue biopsy. While tissue biopsy remains the gold standard, liquid biopsies could be very beneficial where serial sampling is required, such as monitoring disease progression or development of resistance mutations to current targeted therapies. Liquid biopsies also have a potential role in identifying patients at risk of relapse post treatment and as a component of future lung cancer screening protocols. Rapid developments have led to multiple platforms for isolating circulating tumor cells (CTCs) and detecting circulating tumor DNA (ctDNA); however, standardization is lacking, especially in lung carcinoma. Additionally, clonal hematopoiesis of uncertain clinical significance must be taken into consideration in genetic sequencing, as it introduces the potential for false positives. Various biomarkers have been investigated in liquid biopsies; however, in this review, we will concentrate on the current use of ctDNA and CTCs, focusing on the clinical relevance, current and possible future applications and limitations of each.
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Affiliation(s)
- Daniel Di Capua
- Department of Histopathology, St. James’s Hospital, D08NHY1 Dublin, Ireland;
| | - Dara Bracken-Clarke
- Department of Medical Oncology, St. James’ Hospital, D08NHY1 Dublin, Ireland;
| | - Karine Ronan
- Faculty of Medicine, University College Dublin, D04V1W8 Dublin, Ireland;
| | - Anne-Marie Baird
- School of Medicine, Trinity Translational Medicine Institute, Trinity College, D02PN40 Dublin, Ireland;
| | - Stephen Finn
- Department of Histopathology, St. James’s Hospital, D08NHY1 Dublin, Ireland;
- Correspondence:
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15
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Fast fully automatic detection, classification and 3D reconstruction of pulmonary nodules in CT images by local image feature analysis. Biomed Signal Process Control 2021. [DOI: 10.1016/j.bspc.2021.102790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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16
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Derlin T, Bogdanova N, Ohlendorf F, Ramachandran D, Werner RA, Ross TL, Christiansen H, Bengel FM, Henkenberens C. Assessment of γ-H2AX and 53BP1 Foci in Peripheral Blood Lymphocytes to Predict Subclinical Hematotoxicity and Response in Somatostatin Receptor-Targeted Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel) 2021; 13:cancers13071516. [PMID: 33806081 PMCID: PMC8036952 DOI: 10.3390/cancers13071516] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/16/2021] [Accepted: 03/20/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response. METHODS A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (177Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (68Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1. RESULTS DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX+ cells between baseline and +1 h (r = -0.6080; p = 0.0045). Patients showing early development of new metastases had less γ-H2AX (p = 0.0125) and less 53BP1 foci per cell at +1 h (p = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: p = 0.0025; 53BP1: p = 0.0008). CONCLUSIONS Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.
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Affiliation(s)
- Thorsten Derlin
- Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany; (F.O.); (R.A.W.); (T.L.R.); (F.M.B.)
- Correspondence: ; Tel.: +49-(0)5115322579; Fax: +49-(0)5115323761
| | - Natalia Bogdanova
- Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany; (N.B.); (H.C.); (C.H.)
| | - Fiona Ohlendorf
- Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany; (F.O.); (R.A.W.); (T.L.R.); (F.M.B.)
| | - Dhanya Ramachandran
- Department of Radiation Oncology, and Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany;
| | - Rudolf A. Werner
- Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany; (F.O.); (R.A.W.); (T.L.R.); (F.M.B.)
| | - Tobias L. Ross
- Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany; (F.O.); (R.A.W.); (T.L.R.); (F.M.B.)
| | - Hans Christiansen
- Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany; (N.B.); (H.C.); (C.H.)
| | - Frank M. Bengel
- Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany; (F.O.); (R.A.W.); (T.L.R.); (F.M.B.)
| | - Christoph Henkenberens
- Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany; (N.B.); (H.C.); (C.H.)
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Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy. Diagnostics (Basel) 2021; 11:diagnostics11030504. [PMID: 33809226 PMCID: PMC8000284 DOI: 10.3390/diagnostics11030504] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/03/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022] Open
Abstract
Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., C-reactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]Ga-DOTA-TATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (p < 0.001), ANC (p = 0.002), and PCM (p < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (p = 0.0157) and NLR (p = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, p = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; p = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEP-NETs receiving PRRT.
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Liu W, Chen W, Zhang X, Zhao P, Fan Z, Bi L, Wu D, Li S, Yang M, Fu T, Song D, Han B, Zhao G, Du Y, Shi A. Higher efficacy and reduced adverse reactions in neoadjuvant chemotherapy for breast cancer by using pegylated liposomal doxorubicin compared with pirarubicin. Sci Rep 2021; 11:199. [PMID: 33420241 PMCID: PMC7794400 DOI: 10.1038/s41598-020-80415-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 12/21/2020] [Indexed: 12/28/2022] Open
Abstract
The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.
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Affiliation(s)
- Weifang Liu
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Wei Chen
- Department of Breast Surgery, Song Yuan Central Hospital, Changchun, China
| | - Xiuxiang Zhang
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Peng Zhao
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Jining Medical University, Shandong, China
| | - Zhimin Fan
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Lirong Bi
- Department of Pathology, First Hospital of Jilin University, Changchun, China
| | - Di Wu
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Sijie Li
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Ming Yang
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Tong Fu
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Dong Song
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Bing Han
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Gang Zhao
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Ye Du
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
| | - Aiping Shi
- Department of Breast Surgery, First Hospital of Jilin University, Changchun, China.
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Woeste MR, Geller AE, Martin RCG, Polk HC. Optimizing the Combination of Immunotherapy and Trans-Arterial Locoregional Therapy for Stages B and C Hepatocellular Cancer. Ann Surg Oncol 2021; 28:1499-1510. [PMID: 33393028 DOI: 10.1245/s10434-020-09414-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/10/2020] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy worldwide, is the second leading cause of cancer-related death. Underlying liver dysfunction and advanced stage of disease require treatments to be optimally timed and implemented to minimize hepatic parenchymal damage while maximizing disease response and quality of life. Locoregional therapies (LRTs) such as trans-arterial chemo- and radio-embolization remain effective for intermediate liver-only and advanced HCC disease (i.e., Barcelona-Clinic liver cancer stages B and C) not amendable to primary resection or ablation. Additionally, these minimally invasive interventions have been shown to augment the immune system. This and the recent success of immune-oncologic treatments for HCC have generated interest in applying these therapies in combination with such locoregional interventions to improve patient outcomes and response rates. This report reviews the use of trans-arterial LRTs with immunotherapy for stages B and C HCC, potential biomarkers, and imaging methods for assessing the response and safety of such combinations.
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Affiliation(s)
- Matthew R Woeste
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Anne E Geller
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.,Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA.
| | - Hiram C Polk
- Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
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Pediatric Rhabdomyosarcomas: Three-Dimensional Radiological Assessments after Induction Chemotherapy Predict Survival Better than One-Dimensional and Two-Dimensional Measurements. Cancers (Basel) 2020; 12:cancers12123808. [PMID: 33348683 PMCID: PMC7766999 DOI: 10.3390/cancers12123808] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/12/2020] [Accepted: 12/14/2020] [Indexed: 11/16/2022] Open
Abstract
Radiological response to neoadjuvant chemotherapy is currently used to assess the efficacy of treatment in pediatric patients with rhabdomyosarcoma (RMS), but the association between early tumor response on imaging and survival is still controversial. The aim of this study was to investigate the prognostic value of assessing radiological response after induction therapy in pediatric RMS, comparing four different methods. This retrospective, two-center study was conducted on 66 non-metastatic RMS patients. Two radiologists measured tumor size on pre- and post-treatment magnetic resonance (MR) or computed tomography (CT) images using four methods: considering maximal diameter with the 1D-RECIST (Response Evaluation Criteria in Solid Tumors); multiplying the two maximal diameters with the 2D-WHO (World Health Organization); multiplying the three maximal diameters with the 3D-EpSSG (European pediatric Soft tissue sarcoma Study Group); obtaining a software-assisted volume assessment with the 3D-Osirix. Each patient was classified as a responder or non-responder based on the proposed thresholds for each method. Tumor response was compared with survival using Kaplan-Meier plots, the log-rank test, and Cox's regression. Agreement between methods and observers (weighted-κ) was also calculated. The 5-year event-free survival (5yr-EFS) calculated with the Kaplan-Meier plots was significantly longer for responders than for non-responders with all the methods, but the 3D assessments differentiated between the two groups better than the 1D-RECIST or 2D-WHO (p1D-RECIST = 0.018, p2D-WHO = 0.007, p3D-EpSSG and p3D-Osirix < 0.0001). Comparing the 5yr-EFS of responders and non-responders also produced adjusted hazard ratios of 3.57 (p = 0.0158) for the 1D-RECIST, 5.05 for the 2D-WHO (p = 0.0042), 14.40 for the 3D-EpSSG (p < 0.0001) and 11.60 for the 3D-Osirix (p < 0.0001), indicating that the volumetric measurements were significantly more strongly associated with EFS. Inter-method agreement was excellent between the 3D-EpSSG and the 3D-Osirix (κ = 0.98), and moderate for the other comparisons (0.5 < κ < 0.8). The 1D-RECIST and the 2D-WHO tended to underestimate response to treatment. Inter-observer agreement was excellent with all methods (κ > 0.8) except for the 2D-WHO (κ = 0.7). In conclusion, early tumor response was confirmed as a significant prognostic factor in RMS, and the 3D-EpSSG and 3D-Osirix methods predicted response to treatment better than the 1D-RECIST or 2D-WHO measurements.
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21
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Nam SY, Ahn SJ, Jang YR, Chun YS, Park HK, Choi SJ, Choi HY, Kim JH. Diagnostic accuracy of non-contrast abdominopelvic computed tomography scans in follow-up of breast cancer patients. Br J Radiol 2020; 94:20201087. [PMID: 33306919 DOI: 10.1259/bjr.20201087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES To evaluate the effectiveness of follow-up with non-enhanced CT (NECT) in patients with breast cancer. METHODS The present retrospective study included 1396 patients with breast cancer. Group A included patients with no metastasis to evaluate the diagnostic performance of NECT in detecting newly developed metastasis. Group B included patients with known hepatic metastasis to evaluate the accuracy of NECT for the assessment of hepatic metastasis. RESULTS Group A included 895 patients (mean age 52.8 years). Among them, 145 patients had 160 metastases. The per-patient sensitivities for diagnosing newly developed metastasis were 68.3 and 53.8% according to the two reviewers, while the per-lesion sensitivities were 89.4 and 85.0%. Sensitivities for bone metastasis were 98.9 and 95.9%, while sensitivities for hepatic metastasis were 73.7 and 68.4%. In group B, the accuracy of hepatic metastasis response evaluation according to the RECIST criteria was 70.8% for reviewer 1 and 63.8% for reviewer 2. CONCLUSIONS NECT showed inadequate diagnostic performance in detecting newly developed metastasis and in evaluating the response of hepatic metastasis. However, NECT can be utilized as a follow-up modality in patients with decreased renal function or hypersensitivity to iodinated contrast media. ADVANCES IN KNOWLEDGE The risk of side effects of contrast media should be considered as important when NECT can be utilized as a follow-up modality in decreased renal function patients.
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Affiliation(s)
- Sang Yu Nam
- Department of Radiology, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Su Joa Ahn
- Department of Radiology, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Young Rock Jang
- Department of Internal Medicine, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Yong Soon Chun
- Department of Surgery Breast Cancer Center, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Heung Kyu Park
- Department of Surgery Breast Cancer Center, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Seung Joon Choi
- Department of Radiology, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Hye Young Choi
- Department of Radiology, Gil Medical Center of Gachon University, Incheon, South Korea
| | - Jeong Ho Kim
- Department of Radiology, Gil Medical Center of Gachon University, Incheon, South Korea
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22
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Jia B, Zhang X, Mo Y, Chen B, Long H, Rong T, Su X. The Study of Tumor Volume as a Prognostic Factor in T Staging System for Non-Small Cell Lung Cancer: An Exploratory Study. Technol Cancer Res Treat 2020; 19:1533033820980106. [PMID: 33297855 PMCID: PMC7734535 DOI: 10.1177/1533033820980106] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: This study aimed to evaluate T staging system for non-small cell lung cancer (NSCLC) using tumor volume (TV) and other prognostic factors. Methods: This study included 1309 cases. The TV and greatest tumor diameter (GTD) were semi-automatically measured. The receiver operating characteristic (ROC) curves of TV and GTD were used to predict survival. The regression analysis was used to describe the correlation between GTD and TV. Overall survival (OS) was analyzed using the Kaplan-Meier method. Cox’s proportional hazards regression model was applied for multivariate analysis. Results: Using the OS in pN0M0 patients (997 cases), we obtained 4 optimal cutoff values and divided all cases into 5 TV groups (V1: TV ≤ 2.80 cm3; V2: TV > 2.80–6.40 cm3; V3: TV > 6.40–12.9 cm3; V4: TV > 12.9–55.01 cm3; V5: TV > 55.01 cm3) with significant OS (P < 0.001). Multivariate analysis showed that age, visceral pleural invasion (VPI), and all TV cutoff points were independent factors of OS (P < 0.05). For V3 and V4 groups, the OS in patients without VPI was better than that in patients with VPI. Using the values of TV, VPI, and N stages, we classified all cases into 5 stages from I to V depending on the OS. The OS in I, II, III, IV, and V stages were 71.3%, 65.5%, 59.8%, 47.7%, and 35.1% respectively (P < 0.001). Conclusions: We proposed a new T staging system using TV as the main prognostic descriptor in NSCLC patients, which may provide a better comprehensive clinical value than GTD in clinical applications.
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Affiliation(s)
- Bei Jia
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
| | - Xu Zhang
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
| | - Yunxian Mo
- State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Imaging and Interventional Center, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Biao Chen
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
| | - Hao Long
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
| | - Tiehua Rong
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
| | - Xiaodong Su
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China
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23
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Narbe U, Bendahl PO, Aaltonen K, Fernö M, Forsare C, Jørgensen CLT, Larsson AM, Rydén L. The Distribution of Circulating Tumor Cells Is Different in Metastatic Lobular Compared to Ductal Carcinoma of the Breast-Long-Term Prognostic Significance. Cells 2020; 9:E1718. [PMID: 32709042 PMCID: PMC7407940 DOI: 10.3390/cells9071718] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 07/13/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. MATERIALS AND METHODS Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). RESULTS The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. CONCLUSIONS The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.
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Affiliation(s)
- Ulrik Narbe
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
- Department of Oncology, Växjö Central Hospital, SE-352 34 Växjö, Sweden
| | - Pär-Ola Bendahl
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
| | - Kristina Aaltonen
- Department of Laboratory Medicine, Division of Translational Cancer Research, Lund University, SE-223 81 Lund, Sweden;
| | - Mårten Fernö
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
| | - Carina Forsare
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
| | - Charlotte Levin Tykjær Jørgensen
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
| | - Anna-Maria Larsson
- Department of Clinical Sciences, Division of Oncology, Lund University, SE-223 81 Lund, Sweden; (U.N.); (P.-O.B.); (M.F.); (C.F.); (C.L.T.J.); (A.-M.L.)
- Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, SE-221 85 Lund, Sweden
| | - Lisa Rydén
- Department of Clinical Sciences, Division of Surgery, Lund University, SE-223 81 Lund, Sweden
- Department of Surgery, Skåne University Hospital, SE-221 85 Lund, Sweden
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24
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McCarthy CE, White JM, Viola NT, Gibson HM. In vivo Imaging Technologies to Monitor the Immune System. Front Immunol 2020; 11:1067. [PMID: 32582173 PMCID: PMC7280489 DOI: 10.3389/fimmu.2020.01067] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 05/04/2020] [Indexed: 12/13/2022] Open
Abstract
The past two decades have brought impressive advancements in immune modulation, particularly with the advent of both cancer immunotherapy and biologic therapeutics for inflammatory conditions. However, the dynamic nature of the immune response often complicates the assessment of therapeutic outcomes. Innovative imaging technologies are designed to bridge this gap and allow non-invasive visualization of immune cell presence and/or function in real time. A variety of anatomical and molecular imaging modalities have been applied for this purpose, with each option providing specific advantages and drawbacks. Anatomical methods including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound provide sharp tissue resolution, which can be further enhanced with contrast agents, including super paramagnetic ions (for MRI) or nanobubbles (for ultrasound). Conjugation of the contrast material to an antibody allows for specific targeting of a cell population or protein of interest. Protein platforms including antibodies, cytokines, and receptor ligands are also popular choices as molecular imaging agents for positron emission tomography (PET), single-photon emission computerized tomography (SPECT), scintigraphy, and optical imaging. These tracers are tagged with either a radioisotope or fluorescent molecule for detection of the target. During the design process for immune-monitoring imaging tracers, it is important to consider any potential downstream physiologic impact. Antibodies may deplete the target cell population, trigger or inhibit receptor signaling, or neutralize the normal function(s) of soluble proteins. Alternatively, the use of cytokines or other ligands as tracers may stimulate their respective signaling pathways, even in low concentrations. As in vivo immune imaging is still in its infancy, this review aims to describe the modalities and immunologic targets that have thus far been explored, with the goal of promoting and guiding the future development and application of novel imaging technologies.
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Affiliation(s)
- Claire E McCarthy
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Jordan M White
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Nerissa T Viola
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
| | - Heather M Gibson
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
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25
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Broadhurst PJ, Hart AR. An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases. J Cancer Res Clin Oncol 2020; 146:1369-1375. [PMID: 32157435 DOI: 10.1007/s00432-020-03177-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 03/03/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. METHODS Patient notes with PDAC were reviewed at a large teaching hospital over 2 years. Study variables were obtained from multiple sources of information. RESULTS 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. CONCLUSION Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin's pharmacodynamic actions needs to be clarified.
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Affiliation(s)
| | - Andrew R Hart
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
- Norfolk and Norwich University Hospital NHS Trust, Norwich, NR4 7TJ, UK
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26
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Cools KS, Moon AM, Burke LM, McGinty KA, Strassle PD, Gerber DA. Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma. Liver Transpl 2020; 26:203-214. [PMID: 31677319 PMCID: PMC6980979 DOI: 10.1002/lt.25673] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 10/26/2019] [Indexed: 12/17/2022]
Abstract
Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.
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Affiliation(s)
- Katherine S. Cools
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Andrew M. Moon
- Division of Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Lauren M.B. Burke
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Katrina A. McGinty
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Paula D. Strassle
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Department of Epidemiology, University of North Carolina School of Public Health
| | - David A. Gerber
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC
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27
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Figueroa JM, Semonche A, Magoon S, Shah A, Luther E, Eichberg D, Komotar R, Ivan ME. The role of neutrophil-to-lymphocyte ratio in predicting overall survival in patients undergoing laser interstitial thermal therapy for glioblastoma. J Clin Neurosci 2020; 72:108-113. [PMID: 31918907 DOI: 10.1016/j.jocn.2019.12.057] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 11/21/2019] [Accepted: 12/30/2019] [Indexed: 11/30/2022]
Abstract
Laser interstitial thermal therapy (LITT) offers a minimally-invasive treatment option for glioblastomas (GBM) which are relatively small or in eloquent areas. While laser ablation for malignant gliomas has been shown to be safe and effective, the role of the subsequent immune response in not well established. In this study we aim to analyze the prognostic potential of edema volume and acute inflammation, quantified as neutrophil-to-lymphocyte ratio (NLR), in predicting overall survival. Twenty-one patients were identified with new or recurrent GBMs that were candidates for LITT. Laser ablation was performed using standard solid tumor protocol for treatment volume, intensity and duration. Edema volume was quantified using MRI imaging, while retrospective chart review was performed to calculate NLR and survival. In patients treated with LITT for GBM, peri-tumoral vasogenic edema volumes did not significantly change post-operatively, p > 0.200, while NLR significantly increased, p = 0.0002. The degree of NLR increase correlated with longer overall survivals, and ROC analysis demonstrated an area under the curve of 0.827, p = 0.0112. A delta-NLR cutoff of 7.0 results in positive and negative predictive values of 78% and 75%, respectively, in predicting overall survival >1 year. Patients with with delta-NLR > 7.0 lived significantly longer that those with delta-NLR < 7.0, median survival 440 days compared to 239 days, p = 0.0297. We demonstrate preliminary data that monitoring the inflammatory response after LITT in GBM patients offers a potential prognostic measurement to assist in predicting treatment efficacy and overall survival.
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Affiliation(s)
- Javier M Figueroa
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States.
| | - Alexa Semonche
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Stephanie Magoon
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Ashish Shah
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Evan Luther
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Daniel Eichberg
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Ricardo Komotar
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
| | - Michael E Ivan
- Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14(th) Terrace, Miami, FL 33136, United States
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28
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Sa R, Cheng L, Jin Y, Fu H, Shen Y, Chen L. Distinguishing Patients With Distant Metastatic Differentiated Thyroid Cancer Who Biochemically Benefit From Next Radioiodine Treatment. Front Endocrinol (Lausanne) 2020; 11:587315. [PMID: 33304320 PMCID: PMC7701118 DOI: 10.3389/fendo.2020.587315] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 10/21/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Repeated radioiodine (131I) treatment (RT) are commonly performed in patients with 131I-avid distant metastatic differentiated thyroid cancer (DM-DTC), but more precise indications remain indeterminate. This prospective study was conducted to explore predictors for biochemical response (BR) to next RT. METHODS Totally thyroidectomized patients with 131I-avid DM-DTC demonstrated by initial post-therapeutic whole body scan (Rx-WBS) were consecutively recruited. Repeated RTs were performed at a fixed dose and a fixed interval, which was terminated once a decline in thyroid stimulating hormone-suppressed thyroglobulin (Tgon) could not be achieved or Rx-WBS was negative. BR was evaluated by change rate of Tgon level (ΔTgon%). RESULTS After exclusion of 27 ineligible courses, a total of 166 neighboring course pairs from 77 patients were established and utilized. Univariate and multivariate analyses showed that the maximum target/background ratio (T/Bmax) on the whole body scan and ΔTgon% derived from the former RT were independently associated to the latter one. In predicting biochemical remission, the positive predictive value (PPV) and negative predictive value (NPV) of T/Bmax at the cut-off value of 8.1 were 79.1% and 84.0%, respectively; whereas the PPV and NPV of ΔTgon% at the cut-off value of 25.3% were 70.8% and 77.1%, respectively. Notably, the PPV of combined T/Bmax ≥ 8.1 and ΔTgon% ≥ 25.3% increased to 87.7%; while the NPV of T/Bmax ≥ 8.1 or ΔTgon% ≥ 25.3% reached as high as 97.7%. CONCLUSIONS This study revealed that combined use of the latest RT-derived T/Bmax and ΔTgon% may efficiently identify biochemical responders/non-responders to next RT, warranting management optimization of patients with 131I-avid DM-DTC.
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Affiliation(s)
- Ri Sa
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, China
| | - Lin Cheng
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Yuchen Jin
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Hao Fu
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Yan Shen
- Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Yan Shen, ; Libo Chen,
| | - Libo Chen
- Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Yan Shen, ; Libo Chen,
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29
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Lauenstein TC, Schelhorn J, Kinner S. Assessment of Tumor Response with MRI and CT After Radioembolization. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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30
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Roldan CS, Chen JJ, Fareed MM, Hameed MY, Churilla TM, Lango MN, Galloway TJ. Impact of primary tumor-specific growth rate on treatment failure for nonoropharyngeal head and neck cancers. Laryngoscope 2019; 130:2378-2384. [PMID: 31714626 DOI: 10.1002/lary.28393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 09/26/2019] [Accepted: 10/10/2019] [Indexed: 11/08/2022]
Abstract
OBJECTIVES To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC). METHODS The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (< 2.18% per day). RESULTS The median follow-up was 22 months (range: 1-86 months) and median time between diagnostic and simulation computed tomography scans was 22 days (range: 7-170 days). Median RT dose was 70 Gy (range: 60-79.2 Gy). Based on the 75th percentile TSGR, OS at median follow-up was 50.0% for the high TSGR group compared to 92.5% for the low TSGR group (HR [95% confidence interval (CI)] = 2.12[1.16-11.42], P = 0.018). There was a trend toward worse DFS at median follow-up for the high versus low TSGR groups, at 55.6% and 82.3%, respectively (HR [95% CI] = 2.29[0.82-6.38], P = 0.103). CONCLUSION Our study contributes to growing literature on TSGR as a temporal biomarker in patients with non-OPSCC. Patients with high TSGR ≥2.18% per day have significantly worse OS compared to those with TSGR below this threshold. Efforts to address treatment initiation delays may benefit patients with particularly aggressive and rapidly growing tumors. LEVEL OF EVIDENCE 4 Laryngoscope, 130:2378-2384, 2020.
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Affiliation(s)
| | - Jie Jane Chen
- Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts
| | - M Mohsin Fareed
- Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | | | - Thomas M Churilla
- the Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, U.S.A
| | - Miriam N Lango
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, U.S.A
| | - Thomas J Galloway
- the Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, U.S.A
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Zhang X, Su XD. ASO Author Reflections: Which Is a Better Way to Describe Tumor Size of Lung Cancer: Tumor Volume or Diameter? Ann Surg Oncol 2019; 26:790-791. [PMID: 31620940 DOI: 10.1245/s10434-019-07938-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Indexed: 11/18/2022]
Affiliation(s)
- Xu Zhang
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China.,Department of Radiology, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiao-Dong Su
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. .,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, People's Republic of China. .,Department of Radiology, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.
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Abstract
Renal cell cancer is nowadays predominantly diagnosed in early stages due to the widespread use of sectional imaging for unrelated symptoms. Small renal masses (<4 cm) feature a largely indolent biology with a very low risk for metastasis or even a benign biology in up to 30% of the cases. Consequently, there is a need for less invasive therapeutic alternatives to nephron-sparing surgery. Meanwhile, there is a broad portfolio of local ablation techniques to treat small renal tumors. These include the extensively studied radiofrequency ablation and cryoablation techniques as well as newer modalities like microwave ablation and irreversible electroporation as more experimental techniques. Tumor ablation can be performed percutaneously under image guidance or laparoscopically. In particular, the percutaneous approach is a less invasive alternative to nephron-sparing surgery with lower risk for complications. Comparative studies and meta-analyses report a higher risk for local recurrence after renal tumor ablation compared to surgery. However, long-term oncological results after treatment of small renal masses are promising and do not seem to differ from partial nephrectomy. The possibility for salvage therapy in case of recurrence also accounts for this finding. Especially old patients with an increased risk of surgical and anesthesiological complications as well as patients with recurrent and multiple hereditary renal cell carcinomas may benefit from tumor ablation. Tumor biopsy prior to intervention is associated with very low morbidity rates and is oncologically safe. It can help to assess the biology of the renal mass and prevent therapy of benign lesions.
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Yamamichi J, Kawaguchi Y, Otsuka T, Nakashita S, Mizobe H, Eguchi Y, Kimura S. Assessment of tumor volume and density as a measure of the response of advanced hepatocellular carcinoma to sorafenib: Application of automated measurements on computed tomography scans. JGH OPEN 2019; 4:145-152. [PMID: 32280757 PMCID: PMC7144795 DOI: 10.1002/jgh3.12230] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 06/28/2019] [Accepted: 07/01/2019] [Indexed: 12/14/2022]
Abstract
Background and Aim To better predict patient survival, we used automated tumor volume and density measurements to make an objective radiological assessment of the response of advanced hepatocellular carcinoma (HCC) to treatment with sorafenib. Methods Patients treated with sorafenib were identified retrospectively. Those who were diagnosed with Child‐Pugh class A liver function, Barcelona‐Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status grade 0/1 were enrolled (n = 22). Reviews of contrast‐enhanced computed tomography images were supported by the automated measurement of lesions using computer software. Treatment responses were assessed using volume and density criteria. Kaplan–Meier methods and multivariate Cox regression analysis were used to evaluate treatment responses and identify the most significant prognostic factors for overall survival (OS). Results After patients were dichotomized according to volume and density criteria, the median OS for those with an objective response (OR) (complete response + partial response) was 20.4 months and that for those with a non‐OR (stable disease + progressive disease) was 9.3 months (P = 0.009). The best multivariate regression model for survival identified volume and density criteria (OR or non‐OR) as a significant variable, along with baseline alpha‐fetoprotein levels (log‐rank test, P = 0.01). No other conventional criteria were identified as significant. Conclusions Tumor volume and density assessment using automated lesion measurements may be an objective method of evaluating responses of advanced HCC to treatment with sorafenib.
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Affiliation(s)
- Junta Yamamichi
- Medical Equipment Business Planning Department, Medical Systems Operations Canon Inc. Tokyo Japan
| | - Yasunori Kawaguchi
- Department of Hepatobiliary and Pancreatology Saga-ken Medical Centre Koseikan Saga Japan
| | - Taiga Otsuka
- Department of Oncology Saga-ken Medical Centre Koseikan Saga Japan
| | - Shunya Nakashita
- Department of Hepatobiliary and Pancreatology Saga-ken Medical Centre Koseikan Saga Japan
| | - Hideaki Mizobe
- Medical Equipment Business Planning Department, Medical Systems Operations Canon Inc. Tokyo Japan
| | - Yuichiro Eguchi
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan
| | - Shinya Kimura
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan
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Yoo J, Chong S, Lim C, Heo M, Hwang IG. Assessment of spatial tumor heterogeneity using CT growth patterns estimated by tumor tracking on 3D CT volumetry of multiple pulmonary metastatic nodules. PLoS One 2019; 14:e0220550. [PMID: 31369602 PMCID: PMC6675092 DOI: 10.1371/journal.pone.0220550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 07/18/2019] [Indexed: 02/03/2023] Open
Abstract
Purpose Our purpose was to assess the differences in growth rates of multiple pulmonary metastatic nodules using three-dimensional (3D) computed tomography (CT) volumetry and propose a concept of CT spatial tumor heterogeneity. Materials and methods We manually measured the largest diameter of metastatic pulmonary nodules on chest CT scans, and calculated the 3D maximum diameter and the volume using a semi-automated 3D CT volumetry of each nodule. The tumor response was assessed according to the revised RECIST 1.1. We defined a nodule as an outlier based on 1.5 times growth during follow-up. The CT spatial tumor heterogeneity was statistically analyzed by the “minimum combination t-test method” devised in our study. Results On manual measurement, the tumor response category was stable disease (SD) in all 10 patients. Of them, total 155 metastatic nodules (4–52 nodules per patient) were segmented using the 3D CT volumetry. In the 3D maximum diameter, 9 patients had SD except for one patient with partial response in the two selected nodules; for the volume, all 10 patients were SD. For the 3D maximum diameter, six patients had at least one outlier; whereas five patients had the outlier on the volume measurement. Six patients were proven to have overall CT spatial tumor heterogeneity. Conclusions The spatial tumor heterogeneity determined in a CT parametric approach could be statistically assessed. In patients with CT spatial heterogeneity, tumors with different growth rates may be neglected when the nodules are assessed according to the current guideline.
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Affiliation(s)
- Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Semin Chong
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- * E-mail:
| | - Changwon Lim
- Department of Applied Statistics, Chung-Ang University, Seoul, Korea
| | - Miyoung Heo
- Department of Applied Statistics, Chung-Ang University, Seoul, Korea
| | - In Gyu Hwang
- Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
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Xie HJ, Zhang X, Mo YX, Long H, Rong TH, Su XD. Tumor Volume Is Better Than Diameter for Predicting the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer. Ann Surg Oncol 2019; 26:2401-2408. [PMID: 31054041 DOI: 10.1245/s10434-019-07412-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND This study aimed to investigate whether tumor volume (TV) is better than diameter for predicting the prognosis of patients with early-stage non-small cell lung cancer (NSCLC) after complete resection. METHODS This study retrospectively reviewed the clinicopathologic characteristics of 274 patients with early-stage NSCLC who had received pretreatment computed tomography (CT) scans and complete resection. TV was semi-automatically measured from CT scans using an imaging software program. The optimal cutoff of TV was determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. The prognostic significance of TV and other variables was assessed by Cox proportional hazards regression analysis. RESULTS Using 3.046 cm3 and 8.078 cm3 as optimal cutoff values of TV, the patients were separated into three groups. A larger TV was significantly associated with poor DFS and OS in the multivariable analysis. Kaplan-Meier curves of DFS and OS showed significant differences on the basis of TV among patients with stage 1a disease, greatest tumor diameter (GTD) of 2 cm or smaller, and GTD of 2-3 cm, respectively. Using two TV cutoff points, three categories of TV were created. In 54 cases (19.7%), patients migrated from the GTD categories of 2 cm or smaller, 2-3 cm, and larger than 3 cm into the TV categories of 3.046 cm3 or smaller, 3.046-8.078 cm3, and larger than 8.078 cm3. CONCLUSION TV is an independent prognostic factor of DFS and OS for early-stage NSCLC. The findings show that TV is better than GTD for predicting the prognosis of patients with early-stage NSCLC.
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Affiliation(s)
- Hao-Jun Xie
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, China
| | - Xu Zhang
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, China
| | - Yun-Xian Mo
- State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Department of Radiology, Sun Yat Sen University Cancer Center, Guangzhou, China
| | - Hao Long
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, China
| | - Tie-Hua Rong
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China.,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, China
| | - Xiao-Dong Su
- Department of Thoracic Surgery, Sun Yat Sen University Cancer Center, Guangzhou, People's Republic of China. .,State Key Laboratory of Oncology in Southern China and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Lung Cancer Institute, Sun Yat Sen University, Guangzhou, China.
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36
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Patella F, Pesapane F, Fumarola E, Zannoni S, Brambillasca P, Emili I, Costa G, Anderson V, Levy EB, Carrafiello G, Wood BJ. Assessment of the response of hepatocellular carcinoma to interventional radiology treatments. Future Oncol 2019; 15:1791-1804. [PMID: 31044615 DOI: 10.2217/fon-2018-0747] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described.
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Affiliation(s)
- Francesca Patella
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Filippo Pesapane
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Enrico Fumarola
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy.,Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Stefania Zannoni
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | | | - Ilaria Emili
- Postgraduate School of Radiodiagnostics, University of Milan, Milan, Italy
| | - Guido Costa
- Università degli Studi di Milano, Postgraduate School of General Surgery, Milan, Italy
| | - Victoria Anderson
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | - Elliot B Levy
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
| | | | - Bradford J Wood
- Center for Interventional Oncology, National Cancer Institute, NIH, Bethesda, MD, USA
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Kim HD, Kim BJ, Kim HS, Kim JH. Comparison of the morphologic criteria (RECIST) and metabolic criteria (EORTC and PERCIST) in tumor response assessments: a pooled analysis. Korean J Intern Med 2019; 34:608-617. [PMID: 29334722 PMCID: PMC6506740 DOI: 10.3904/kjim.2017.063] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 07/10/2017] [Accepted: 07/19/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND/AIMS The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria are used to assess metabolic tumor responses. However, tumor responses have shown considerable discrepancies between the morphologic criteria (Response Evaluation Criteria in Solid Tumors [RECIST]) and metabolic criteria. We performed this pooled study to compare the RECIST and metabolic criteria in the assessment of tumor responses. METHODS Electronic databases were searched for eligible articles with the terms "RECIST," "PERCIST," or "EORTC criteria." The level of concordance in the tumor responses between the two criteria was estimated using κ statistics. RESULTS A total of 216 patients were collected from eight studies comparing the RECIST and EORTC criteria. The agreement of tumor responses between the two criteria was moderate (κ = 0.447). Eighty-six patients (39.8%) showed disagreement: tumor response was upgraded in 70 patients and downgraded in 16 when adopting the EORTC criteria. The EORTC criteria significantly increased the overall response rate (53% vs. 28%, p < 0.0001). The agreement of tumor responses between the RECIST and PERCIST was deemed fair (κ = 0.389). Of 407 patients from nine studies, 181 (44.5%) showed a discrepancy: using the PERCIST, tumor response were upgraded in 151 patients and downgraded in 30. When adopting the PERCIST, the overall response rate was also significantly increased from 30% to 55% (p < 0.0001). CONCLUSION This pooled analysis demonstrates that the concordance of tumor responses between the morphologic criteria and metabolic criteria is not excellent. When adopting the metabolic criteria instead of the RECIST, overall response rates were significantly increased.
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Affiliation(s)
- Hong Deok Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Bum Jun Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Hyeong Su Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | - Jung Han Kim
- Division of Hemato-Oncology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
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Tian J, Geng Y, Lv D, Li P, Cordova M, Liao Y, Tian X, Zhang X, Zhang Q, Zou K, Zhang Y, Zhang X, Li Y, Zhang J, Ma Z, Shao Y, Song L, Owen GI, Li T, Liu R, Liu Q, Zou L, Zhang Z, Li Z. Using plasma cell-free DNA to monitor the chemoradiotherapy course of cervical cancer. Int J Cancer 2019; 145:2547-2557. [PMID: 30919951 DOI: 10.1002/ijc.32295] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 02/10/2019] [Accepted: 03/12/2019] [Indexed: 12/16/2022]
Abstract
The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell-free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer.
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Affiliation(s)
- Jichao Tian
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Yan Geng
- Department of Radiotherapy, Ansteel Group Hospital, Anshan, Liaoning, China
| | - Dekang Lv
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Peiying Li
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Miguel Cordova
- Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Yuwei Liao
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Xiaoyuan Tian
- The Second Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Xiaolong Zhang
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Qingzheng Zhang
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Kun Zou
- The first affiliated hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Yu Zhang
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Xia Zhang
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Yulong Li
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Jian Zhang
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Zhaokui Ma
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Yanyan Shao
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Luyao Song
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Gareth I Owen
- Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Tingting Li
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Ruimei Liu
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Quentin Liu
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
| | - Lijuan Zou
- The Second Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Zhuo Zhang
- The Second Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Zhiguang Li
- Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China
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Radiology reporting of low-grade glioma growth underestimates tumor expansion. Acta Neurochir (Wien) 2019; 161:569-576. [PMID: 30756242 DOI: 10.1007/s00701-018-03783-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 12/19/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND An important aspect in the management of patients with diffuse low-grade gliomas (LGGs) involves monitoring the lesions via serial magnetic resonance imaging (MRI). However, radiological interpretations of LGG interval scans are often qualitative and thus difficult to use clinically. METHODS To contextualize these assessments, we retrospectively compared radiological interpretations of LGG growth or stability to volume change measured by manual segmentation. Tumor diameter was also measured in one, two, and three dimensions to evaluate reported methods for assessment of glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumor diameter/ellipsoid method. RESULTS Tumors evaluated as stable by radiologists grew a median volume of 5.1 mL (11.1%) relative to the comparison scan, and those evaluated as having grown had a median volume increase of 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate gold standard segmented volumes. In addition, agreement with segmented volume measurements improved from 17.6 ± 8.0 to 4.5 ± 5.8 to 3.9 ± 3.6 mm for diameter and from 104.0 ± 96.6 to 25.3 ± 36.8 to 15.9 ± 21.3 mL for volume with radiological measurements in one, two, and three dimensions, respectively. Measurement overestimation increased with tumor size. CONCLUSIONS Given accumulating evidence that LGG volume and growth are prognostic factors, there is a need for objective lesion measurement. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. While volumetric analysis remains the gold standard for assessment of growth, careful diametric measurements in three dimensions may be an acceptable alternative.
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40
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Hu S, Pan L, Shangguan J, Figini M, Eresen A, Sun C, Wang B, Ma Q, Hu C, Yaghmai V, Velichko Y, Yang J, Zhang Z. Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras G12D/+;LSL-Trp53 R172H/+;Pdx-1-Cre (KPC) transgenic mouse model. J Immunol Methods 2019; 465:1-6. [PMID: 30468734 DOI: 10.1016/j.jim.2018.11.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 11/19/2018] [Accepted: 11/19/2018] [Indexed: 02/07/2023]
Abstract
The LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 ± 2.9 weeks with a relatively short life span (6.8 ± 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 ± 1.18 mm (range, 2.18-5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 ± 0.52 mm/week) and tumor volume (148.77 ± 80.87 mm3)/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = -0.825, P = .043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.
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Affiliation(s)
- Su Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Liang Pan
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Radiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China
| | - Junjie Shangguan
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Matteo Figini
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Aydin Eresen
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Chong Sun
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Orthopedic, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Bin Wang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Quanhong Ma
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China
| | - Vahid Yaghmai
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA
| | - Yuri Velichko
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA
| | - Jia Yang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
| | - Zhuoli Zhang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
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Does Systemic Administration of Parathyroid Hormone After Noninstrumented Spinal Fusion Surgery Improve Fusion Rates and Fusion Mass in Elderly Patients Compared to Placebo in Patients With Degenerative Lumbar Spondylolisthesis? Spine (Phila Pa 1976) 2019; 44:157-162. [PMID: 30005049 DOI: 10.1097/brs.0000000000002791] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Prospective, randomized, double-blinded, placebo-controlled clinical trial. OBJECTIVE To evaluate whether 90-day subcutaneous injections with 20 μg teriparatide increases the volume and quality of the fusion mass compared to placebo based on 12-month postop fine cut computed tomography scans. The secondary objective is to evaluate whether parathyroid hormone (PTH) increases fusion rates compared to placebo. SUMMARY OF BACKGROUND DATA Few studies have investigated the effects of PTH on fusion in patients undergoing spinal arthrodesis. Early studies showed a more robust fusion mass with PTH after spinal fusion surgery. But the efficiency of PTH on noninstrumented spinal fusion surgery remains unclear. METHODS Patients with degenerative spondylolisthesis scheduled for noninstrumented posterolateral fusion were randomized to receive 90-day subcutaneous injections with 20 μg teriparatide (N = 41) or placebo (N = 46) in a 1:1 fashion. Fusion volume and quality was evaluated using 12-month postoperative fine cut computed tomography scans. RESULTS The two groups were comparable in terms of age, sex, and numbers of levels operated. PTH treatment was well tolerated but provided no additional benefit versus placebo. Fusion rates, the mean volume, and robustness of the fusion mass were similar between the PTH and placebo groups. CONCLUSION Ninety-day subcutaneous administration of 20 μg teriparatide did not increase fusion volume or improve the quality of the fusion mass in elderly patients compared to placebo after noninstrumented spinal fusion surgery for degenerative spondylolisthesis. LEVEL OF EVIDENCE 1.
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Hussein RS, Tantawy W, Abbas YA. MRI assessment of hepatocellular carcinoma after locoregional therapy. Insights Imaging 2019; 10:8. [PMID: 30694398 PMCID: PMC6352610 DOI: 10.1186/s13244-019-0690-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 01/03/2019] [Indexed: 12/16/2022] Open
Abstract
Liver cirrhosis and hepatocellular carcinoma (HCC) constitute one of the major causes of morbidity, mortality, and high health care costs worldwide. Multiple treatment options are available for HCC depending on the clinical status of the patient, size and location of the tumor, and available techniques and expertise. Locoregional treatment options are multiple. The most challenging part is how to assess the treatment response by different imaging modalities, but our scope will be assessing the response to locoregional therapy for HCC by MRI. This will be addressed by conventional MR methods using LI-RADS v2018 and by functional MR using diffusion-weighted imaging, perfusion, and highlighting the value of the novel intravoxel incoherent motion (IVIM).
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Affiliation(s)
- Rasha S Hussein
- Radiology Department, Faculty of Medicine, Ain Shams University and MR Unit of Misr Radiology Center, Cairo, Egypt.
| | - Wahid Tantawy
- Radiology Department, Faculty of Medicine, Ain Shams University and MR Unit of Misr Radiology Center, Cairo, Egypt
| | - Yasser A Abbas
- Radiology Department, Faculty of Medicine, Ain Shams University and MR Unit of Misr Radiology Center, Cairo, Egypt
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43
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Gering D, Sun K, Avery A, Chylla R, Vivekanandan A, Kohli L, Knapp H, Paschke B, Young-Moxon B, King N, Mackie T. Semi-automatic Brain Tumor Segmentation by Drawing Long Axes on Multi-plane Reformat. BRAINLESION: GLIOMA, MULTIPLE SCLEROSIS, STROKE AND TRAUMATIC BRAIN INJURIES 2019. [DOI: 10.1007/978-3-030-11726-9_39] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Borcoman E, Nandikolla A, Long G, Goel S, Le Tourneau C. Patterns of Response and Progression to Immunotherapy. Am Soc Clin Oncol Educ Book 2018; 38:169-178. [PMID: 30231380 DOI: 10.1200/edbk_200643] [Citation(s) in RCA: 160] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Patterns of response and progression to immunotherapy may differ from those observed with drugs such as chemotherapy and molecularly targeted agents. Specifically, some patients experience a response after progression that is retrospectively named pseudoprogression. This phenomenon of pseudoprogression, first reported in patients with melanoma who were treated with ipilimumab, has led to the development of immune-specific related response criteria, such as irRC (immune-related response criteria), irRECIST (immune-related RECIST), and iRECIST (immunotherapy RECIST) that allow continued treatment beyond progression. However, the rate of pseudoprogression has never exceeded 10% of patients across tumor types. Conversely, rapid progressions after immunotherapy, called hyperprogressions, were reported by three different teams in 9% to 29% of patients treated with immunotherapy. Because of the absence of control arms in these studies, it remains to be determined whether these rapid progressions reflect a detrimental effect of immunotherapy in these patients. Finally, preliminary data suggest that immunotherapy might also affect response to subsequent standard therapies. In total, given the rarity of pseudoprogressions across tumor types and the recent description of hyperprogressions, classic RECIST remains a reasonable and rational method to assess response to immunotherapy. Continuation of treatment beyond progression should be proposed only in carefully selected patients whose clinical conditions have improved and who have not experienced severe toxicities. Although there is an urgent need to identify predictive biomarkers of efficacy to immunotherapy, there is an equally urgent need to identify predictive factors of progression or possibly hyperprogression.
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Affiliation(s)
- Edith Borcoman
- From the Department of Drug Development and Innovation, Institut Curie, Paris and Saint-Cloud, France; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Melanoma Institute Australia, North Sydney, NSW, Australia; INSERM U900 Research Unit, Saint-Cloud, France; Versailles Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France
| | - Amara Nandikolla
- From the Department of Drug Development and Innovation, Institut Curie, Paris and Saint-Cloud, France; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Melanoma Institute Australia, North Sydney, NSW, Australia; INSERM U900 Research Unit, Saint-Cloud, France; Versailles Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France
| | - Georgina Long
- From the Department of Drug Development and Innovation, Institut Curie, Paris and Saint-Cloud, France; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Melanoma Institute Australia, North Sydney, NSW, Australia; INSERM U900 Research Unit, Saint-Cloud, France; Versailles Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France
| | - Sanjay Goel
- From the Department of Drug Development and Innovation, Institut Curie, Paris and Saint-Cloud, France; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Melanoma Institute Australia, North Sydney, NSW, Australia; INSERM U900 Research Unit, Saint-Cloud, France; Versailles Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France
| | - Christophe Le Tourneau
- From the Department of Drug Development and Innovation, Institut Curie, Paris and Saint-Cloud, France; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Melanoma Institute Australia, North Sydney, NSW, Australia; INSERM U900 Research Unit, Saint-Cloud, France; Versailles Saint-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France
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Zhang L, Wang N, Mao J, Liu X, Gao Z, Dai X, Feng B. Dual-Energy CT-Derived Volumetric Iodine Concentration for the Assessment of Therapeutic Response after Microwave Ablation in a Rabbit Model with Intrahepatic VX2 Tumor. J Vasc Interv Radiol 2018; 29:1455-1461. [PMID: 30217747 DOI: 10.1016/j.jvir.2018.04.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 04/12/2018] [Accepted: 04/16/2018] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To evaluate whether changes in volumetric iodine concentration (VIC) could serve as a suitable predictor of therapeutic response to microwave (MW) ablation in a rabbit intrahepatic VX2 tumor model. MATERIALS AND METHODS Sixteen intrahepatic VX2 tumors were transplanted in 8 New Zealand White rabbits treated with MW ablation. Contrast-enhanced dual-energy CT scans were obtained at baseline and follow-up. Therapeutic response assessment by modified Response Evaluation Criteria In Solid Tumors (mRECIST), Choi criteria, and VIC changes was performed. An intraclass correlation coefficient (ICC) was used to characterize consistency of assessment results among the criteria used. Technical success was evaluated with explant pathologic findings as a reference. Correlations between technical success and variations in diameter, CT density, and VIC were analyzed. RESULTS Disease control was observed in 4, 8, and 10 of the 16 tumors per mRECIST, Choi criteria, and VIC changes, respectively. VIC exhibited strong consistency (ICC = 0.807, P < .0001) with Choi criteria. According to explant pathology, technical success was achieved in 10 of the 16 tumors. There was a moderate correlation between VIC changes and technical success (r = 0.532, P = .034), and no correlation was found between technical success and variations in diameter or CT density. CONCLUSIONS Compared with mRECIST and Choi criteria, dual-energy CT-derived VIC allowed for better prediction of therapeutic response after MW ablation and could provide a potential imaging biomarker of tumor response to MW ablation in patients with hepatocellular carcinoma.
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Affiliation(s)
- Liang Zhang
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China
| | - Na Wang
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China
| | - Jingsong Mao
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China
| | - Xiaofei Liu
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China
| | - Zhichun Gao
- Department of Biological Technology, China Medical University-The Queen's University of Belfast Joint College, Shenyang, P.R. China
| | - Xu Dai
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China
| | - Bo Feng
- Department of Radiology, The First Affiliated Hospital of China Medical University, 155 Nanjingbei St., Shenyang, Liaoning 110001, P.R. China.
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Pandey A, Pandey P, Aliyari Ghasabeh M, Najmi Varzaneh F, Shao N, Khoshpouri P, Zarghampour M, Fouladi DF, Liddell R, Kamel IR. Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival. Radiology 2018; 288:109-117. [DOI: 10.1148/radiol.2018171593] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Ankur Pandey
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Pallavi Pandey
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Mounes Aliyari Ghasabeh
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Farnaz Najmi Varzaneh
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Nannan Shao
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Pegah Khoshpouri
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Manijeh Zarghampour
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Daniel Fadaei Fouladi
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Robert Liddell
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
| | - Ihab R. Kamel
- From the Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Room 143, Baltimore, MD 21287
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Young S, Taylor AJ, Sanghvi T. Post Locoregional Therapy Treatment Imaging in Hepatocellular Carcinoma Patients: A Literature-based Review. J Clin Transl Hepatol 2018; 6:189-197. [PMID: 29951364 PMCID: PMC6018307 DOI: 10.14218/jcth.2017.00059] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 12/14/2017] [Accepted: 12/22/2017] [Indexed: 12/19/2022] Open
Abstract
Imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as well as in determining treatment efficacy, or complications, following therapy. Unlike other cancers, HCC is most commonly treated by locoregional therapies (LRTs) such as thermal ablation, transarterial chemoembolization, and transarterial radioembolization. These treatments can lead to changes on imaging that make determination of residual/recurrent disease difficult. This literature-based review discusses the expected postimaging findings following LRT.
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Affiliation(s)
- Shamar Young
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
| | - Andrew J. Taylor
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
- *Correspondence to: Andrew J. Taylor, Department of Radiology, University of Minnesota, 420 Delaware Street SE, MMC 292, Minneapolis, MN 55455, USA. Tel: +1-612-626-6638, Fax: +1-612-626-5505, E-mail:
| | - Tina Sanghvi
- Department of Radiology, University of Minnesota, Minneapolis, MN, USA
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Alhanafy A, Abdullah MS, Hafez H, Abbas H. Non Size Based Morphology Criteria for Assessment of Response in Patients with Liver Metastases of Gastrointestinal Origin Receiving Systemic Treatment. Asian Pac J Cancer Prev 2018; 19:1655-1660. [PMID: 29938450 PMCID: PMC6103575 DOI: 10.22034/apjcp.2018.19.6.1655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background and Aim: Liver is the main site of metastases of gastrointestinal cancers, chemotherapy with or without targeted therapy is the standard treatment. Radiologic assessment of tumor response is usually done by the use of Response Evaluation Criteria in Solid Tumor (RECIST) criteria. RECIST depends on tumor size changes but it does not address morphologic changes as overall attenuation, enhancement and tumor liver interface changes which may shown early before tumor size changes. We aimed to evaluate use of contrast enhanced computed tomography (CECT) new morphologic criteria in assessment of response in patients with hepatic metastases of gastrointestinal origin. Methods: This study was carried out by cooperation between Clinical Oncology and Nuclear Medicine and Radiodiagnosis Departments, Faculty of Medicine, Menoufia University. During the period from April 2015 to December 2016 forty patients with stage IV gastrointestinal cancers with hepatic metastases were included, CECT was done before and after systemic treatment, response evaluation was done by RECIST 1.1 and morphology response criteriac. Results: By RECIST, partial response (PR) observed in 57.5%, stable disease (SD) 22.5% and progressive disease (PD) in 20% of patients compared to Optimal response 42.5%, incomplete response 35% and no response in 22.5% of patients by Morphologic response criteria. Regarding survival, patients with PR had median survival of 20 months (95% CI, 17.988 to 22.012months) versus 11 months (95% CI, 1.235 to 8.580 months) in SD or PD by RECIST, (P=.002). while by morphology response criteria the median overall survival of optimally responded patients 23 months (95% CI, 20.04 to 27.81months) versus 16 months (95% CI, 5.590 to 5.044 months) in patients with incomplete or no morphologic response (P=.001). Conclusion: Morphologic response criteria are accurate method for assessment of response of hepatic metastases and correlated well with patients’ survival and better to be incorporated to treatment evaluation.
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Affiliation(s)
- Alshimaa Alhanafy
- Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Menoufia University, Sheben Elkom, Egypt.
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Liu J, Zhang W, Gu M, Ji Y, Yang L, Cheng X, Xiao X, Xu J, Gu C, Zhang J, Zhang S, Chen D, Pan S. Serum SP70 is a sensitive predictor of chemotherapy response in patients with advanced nonsmall cell lung cancer. Cancer Med 2018; 7:2925-2933. [PMID: 29767438 PMCID: PMC6051171 DOI: 10.1002/cam4.1555] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/09/2018] [Accepted: 04/23/2018] [Indexed: 12/15/2022] Open
Abstract
SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P < .001) and increased in the progressive disease (PD) group (P < .001), but not significantly changed in the stable disease (SD) group (P = .114). Although similar changes were observed on CEA and CYFRA21-1 levels but not NSE, ROC analysis demonstrated that SP70 is superior to the others. Additionally, patients with EGFR mutation had higher serum SP70 levels and tissue SP70 expression than patients without EGFR mutation (P = .014 and P = .002, respectively). The median PFS of patients with decreased SP70 levels after chemotherapy was longer than that of patients with stable or increased serum SP70 level (24 months vs 12 months vs 2 months, P < .001), and the differences of all other 3 tumor markers were not obvious. Serum SP70 is a sensitive and real-time indicator of chemotherapeutic efficacy in patients with advanced NSCLC and related to PFS.
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Affiliation(s)
- Jingping Liu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Wei Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Yazhou Ji
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Lu Yang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Xiangjun Cheng
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Xuelian Xiao
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Jian Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Chunrong Gu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Jiexin Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Shichang Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Dan Chen
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
| | - Shiyang Pan
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, China
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Somarouthu B, Lee SI, Urban T, Sadow CA, Harris GJ, Kambadakone A. Immune-related tumour response assessment criteria: a comprehensive review. Br J Radiol 2018; 91:20170457. [PMID: 29172675 PMCID: PMC5966001 DOI: 10.1259/bjr.20170457] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 11/15/2017] [Accepted: 11/21/2017] [Indexed: 12/15/2022] Open
Abstract
Growing emphasis on precision medicine in oncology has led to increasing use of targeted therapies that encompass a spectrum of drug classes including angiogenesis inhibitors, immune modulators, signal transduction inhibitors, DNA damage modulators, hormonal agents etc. Immune therapeutic drugs constitute a unique group among the novel therapeutic agents that are transforming cancer treatment, and their use is rising. The imaging manifestations in patients on immune therapies appear to be distinct from those typically seen with conventional cytotoxic therapies. Patients on immune therapies may demonstrate a delayed response, transient tumour enlargement followed by shrinkage, stable size, or initial appearance of new lesions followed by stability or response. These newer patterns of response to treatment have rendered conventional criteria such as World Health Organization and response evaluation criteria in solid tumours suboptimal in monitoring changes in tumour burden. As a consequence, newer imaging response criteria such as immune-related response evaluation criteria in solid tumours and immune-related response criteria are being implemented in many trials to effectively monitor patients on immune therapies. In this review, we discuss the traditional and new imaging response criteria for evaluation of solid tumours, review the outcomes of various articles which compared traditional criteria with the new immune-related criteria and discuss pseudo-progression and immune-related adverse events.
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Affiliation(s)
| | - Susanna I Lee
- Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
| | - Trinity Urban
- Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Centre, Boston, MA, USA
| | - Cheryl A Sadow
- Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA
| | - Gordon J Harris
- Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Centre, Boston, MA, USA
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