LungStage. Bringing machine learning to Nuclear Medicine and Lung Cancer using Big Data, Machine Learning and Multicenter Studies

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LungStage Bringing machine learning to Nuclear Medicine and Lung Cancer using Big Data, Machine Learning and Multicenter Studies Medical Team: Bram Stieltjes, MD PhD; Alex Sauter, MD; Gregor Sommer, MD; Thomas Weikart, MD AI Team: Kevin Mader, PhD; Joshy Cyriac Experience Team: Flavio Trolese, Joachim Hagger

Conflicts of Interest 4Quant Ltd. Founder / Shareholder

American Cancer Society 2016

What does staging mean? Categorizing the severity of the disease 5 levels for the tumor 4 levels for the lymph nodes 2 levels for metastases 8 different stages for treatment planning 40 different possible categories #SIIM17 American Cancer Society 2016

Why automate staging? Mis-staging patients can have serious consequences as both under and over treating can drastically affect patient health Currently two physicians take over an hour to perform the initial assessment Reports are often incomplete or missing key information

Just Deep Learn! ImageNet 59K pixels per image 1.2M images 0.04 variables (pixels) per example 1200 examples per category LungStage 157M pixels per patient 2000 patients 78,000 variables (pixels) per example (3.9M times worse) 50 examples per category (24 times worse)

We need to learn smart Focus the algorithms on the pixels that are important Most of them aren t < 0.02%

Smart Learning ImageNet 59K pixels per image 1.2M images 0.04 variables per example 1200 examples per category LungStage (+Annotations) ~4000 pixels per patient 2000 patients 2 variables (pixels) per example (50 times worse) 50 examples per category (24 times worse)

Current Status 282 patients >2,000 lesions

Beyond Standard Deep Learning Neural Networks that won image net found categories of images A cat in the corner is the same as a cat in the middle Medicine is different A bulge in the lung isn t the same as a bulge in your knee A spot on your arm could be a life-threatening metastases or an FDG tracer injection site

Beyond Standard Deep Learning Learn, Unlearn and Relearn Contests are much easier than clinical medicine Real data is messy, noisy, poorly structured, missing Many networks work brilliantly under controlled conditions, but fail the simplest of sanity checks #SIIM17 https://www.kaggle.com/kmader/simple-nn-with-keras

Architectures Nobody really knows what works best so gotta try them all. A good cross validation method is essential for figuring out which models learn well

Current Status Each network can take up to 12 hours to train >10,000 different network structures Finding the best will still take some time, but in the meantime, good enough will work >4 billion calculations per patient

Communicating Results As important as making a classification is delivering the confidence in the classification. Neural networks are naturally very bad at this, but Bayesian Networks and simpler models can help

Constructing Simple Rules Our Results T1 T1a T1b T2 T2a T2b T3 T4 Tumor 3 cm across its greatest dimension, surrounded pleura, without invasion, and more proximal than the lobar b Tumor 2 cm across its greatest dimension Tumor >2 cm and 3 cm across its greatest dimension Tumor >3 cm and 7 cm or with any of the following fea bronchus and is more than 2 cm distal to the carina; inva associated with atelectasis or obstructive pneumonitis that region without involvement of the entire lung Tumor >3 cm and 5 cm across its greatest dimension Tumor >5 cm and 7 cm across its greatest dimension Tumor >7 cm or any of the following features: direct invas (including the superior sulcus), diaphragm, phrenic nerve, or parietal pericardium; involvement of the main bronchus carina (without involvement of the carina); associated atele pneumonitis of the entire lung; or a tumor nodule within th of the primary tumor Tumor of any size with invasion of the mediastinum, h trachea, recurrent laryngeal nerve, esophagus, vertebral b separate tumor nodule within an ipsilateral lobe

Constructing Simple Rules Our Results N0 N1 N2 N3 No regional lymph node metastasis Metastasis in ipsilateral peribronchial or ipsilateral hilar and intrapulmonary lymph nodes, including direct extension Metastasis in ipsilateral mediastinal or subcarinal lymph nodes Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral, contralateral scalene, or supraclavicular lymph nodes

Constructing Simple Rules Our Results N0 N1 N2 N3 No regional lymph node metastasis Metastasis in ipsilateral peribronchial or ipsilateral hilar and intrapulmonary lymph nodes, including direct extension Metastasis in ipsilateral mediastinal or subcarinal lymph nodes Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral, contralateral scalene, or supraclavicular lymph nodes

Interactive Tools

Unrolling results to text LungStage found 20 suspicious tumor regions and decided on T4 because of the shown lesions which are invasive in the mediastinum

Next Steps We are looking to involve other hospitals and health-systems We want to further improve the diagnosis of lung cancer. We want to led radiologists make our models better (make code better by giving feedback and using the tools)

Team