Dataset Information

Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

ABSTRACT: Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.

SUBMITTER: Pan C

PROVIDER: S-EPMC7591821 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Pan Chenchen C Schoppe Oliver O Parra-Damas Arnaldo A Cai Ruiyao R Todorov Mihail Ivilinov MI Gondi Gabor G von Neubeck Bettina B Böğürcü-Seidel Nuray N Seidel Sascha S Sleiman Katia K Veltkamp Christian C Förstera Benjamin B Mai Hongcheng H Rong Zhouyi Z Trompak Omelyan O Ghasemigharagoz Alireza A Reimer Madita Alice MA Cuesta Angel M AM Coronel Javier J Jeremias Irmela I Saur Dieter D Acker-Palmer Amparo A Acker Till T Garvalov Boyan K BK Menze Bjoern B Zeidler Reinhard R Ertürk Ali A

Cell 20191201 7

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice ...[more]

PMID: 31835038

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Project description:ImportanceOccult peritoneal metastasis frequently occurs in patients with advanced gastric cancer and is poorly diagnosed with currently available tools. Because the presence of peritoneal metastasis precludes the possibility of curative surgery, there is an unmet need for a noninvasive approach to reliably identify patients with occult peritoneal metastasis.ObjectiveTo assess the use of a deep learning model for predicting occult peritoneal metastasis based on preoperative computed tomography images.Design, setting, and participantsIn this multicenter, retrospective cohort study, a deep convolutional neural network, the Peritoneal Metastasis Network (PMetNet), was trained to predict occult peritoneal metastasis based on preoperative computed tomography images. Data from a cohort of 1225 patients with gastric cancer who underwent surgery at Sun Yat-sen University Cancer Center (Guangzhou, China) were used for training purposes. To externally validate the model, data were collected from 2 independent cohorts comprising a total of 753 patients with gastric cancer who underwent surgery at Nanfang Hospital (Guangzhou, China) or the Third Affiliated Hospital of Southern Medical University (Guangzhou, China). The status of peritoneal metastasis for all patients was confirmed by pathological examination of pleural specimens obtained during surgery. Detailed clinicopathological data were collected for each patient. Data analysis was performed between September 1, 2019, and January 31, 2020.Main outcomes and measuresThe area under the receiver operating characteristic curve (AUC) and decision curve were analyzed to evaluate performance in predicting occult peritoneal metastasis.ResultsA total of 1978 patients (mean [SD] age, 56.0 [12.2] years; 1350 [68.3%] male) were included in the study. The PMetNet model achieved an AUC of 0.946 (95% CI, 0.927-0.965), with a sensitivity of 75.4% and a specificity of 92.9% in external validation cohort 1. In external validation cohort 2, the AUC was 0.920 (95% CI, 0.848-0.992), with a sensitivity of 87.5% and a specificity of 98.2%. The discrimination performance of PMetNet was substantially higher than conventional clinicopathological factors (AUC range, 0.51-0.63). In multivariable logistic regression analysis, PMetNet was an independent predictor of occult peritoneal metastasis.Conclusions and relevanceThe findings of this cohort study suggest that the PMetNet model can serve as a reliable noninvasive tool for early identification of patients with clinically occult peritoneal metastasis, which will inform individualized preoperative treatment decision-making and may avoid unnecessary surgery and complications. These results warrant further validation in prospective studies.

Dataset Information

Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Publications

Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

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