Abstract 5055: Precise segmentation of growth patterns in TRACERx lung adenocarcinoma
Authors: Pan Xiaoxi , Zhang Hanyun , Grapa Anca-Ioana , AbdulJabbar Khalid , Raza Shan E. Ahmed , CHEUNG HO KWAN ALVIN , Karasaki Takahiro , Quesne John Le , Moore David A. , Swanton Charles , Yuan Yinyin 
Published: June 2022

Abstract
Histologic growth patterns are associated with patient prognosis, thus recognized as an important part of the WHO classification in lung adenocarcinoma (Travis et al. 2015, Moreira et al., 2020). The wide spectrum of growth patterns proves challenging for reproducible and quantitative scoring. Currently, scoring is based on manual identification of the predominant pattern and percentages of patterns in routine diagnostic slides. The lack of an automated method also limits our ability to investigate the immune microenvironment of growth patterns.
To overcome the above challenges, we present a deep learning method, Pyramid Stream Networks, to precisely segment growth patterns at pixel level. Unlike existing methods, the proposed method captures different spatial scales of the histology information by novel attention strategies at different learning stages. This problem-oriented design yields precise boundaries for each pattern, enabling the investigation of growth pattern heterogeneity, and the relationship with tumor microenvironment components.
Experiments were conducted on 49 haematoxylin and eosin whole slide images (WSIs) from TRACERx 100 cohort (AbdulJabbar et al., 2020). Each WSI was sparsely annotated by 3 senior pathologists. A total of 2968 annotated patches were split into 5 folds for cross validation. We compared our method with two state-of-the-art methods applied in semantic segmentation, attention U-net (Oktay et al. 2018) and DeepLabV3+ (Chen et al. 2018). When evaluated at patch level, our method outperformed the better comparison method, DeepLabV3+, by 3.43% and 2.99% in pixel-wise Dice and overall precision (OP) (Dice: 60.34% vs. 56,91%, OP: 65.43% vs. 62.44%). When applied to WSIs, the model correctly predicted the predominant pattern for 38 out of 49 samples, achieving an accuracy of 77.55%. Interestingly, in the 11 discordant cases, 10 showed high intra-tumor heterogeneity of growth patterns, measured by Shannon diversity, highlighting the impact of intra-tumor heterogeneity on growth pattern assessment. Additionally, we combined the identified growth patterns with lymphocytic distribution measured in (AbdulJabbar et al., 2020) and revealed a significantly increased immune infiltration in proximity to the solid pattern as compared to others, which is in line with previous findings (Tavernari et al., 2021).
In summary, by leveraging image-analysis and artificial intelligence techniques, we propose a new method for precise growth pattern segmentation from routine histology samples of lung adenocarcinoma. It provides quantitative and reproducible scores of growth patterns, which can be developed into a decision support system for pathologists and clinicians. Furthermore, through pattern-specific spatial mapping, it enables future studies of intra-tumor heterogeneity, such as the preferential infiltration of lymphocyte subsets adjacent to diverse growth patterns.
Citation Format: Xiaoxi Pan, Hanyun Zhang, Anca-Ioana Grapa, Khalid AbdulJabbar, Shan E. Ahmed Raza, HO KWAN ALVIN CHEUNG, Takahiro Karasaki, John Le Quesne, David A. Moore, Charles Swanton, Yinyin Yuan. Precise segmentation of growth patterns in TRACERx lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5055.