Feature-driven local cell graph (FLocK): New computational pathology-based descriptors for prognosis of lung cancer and HPV status of oropharyngeal cancers

e15502 Background: HPV status of anal and vulvar cancers cannot be predicted by visual inspection as well as for oropharyngeal cancers. Radiomics applied on computed tomography images can extract features that may better characterize the structure and the underlying biology of the tumor. Methods: In this multi-center study, we validated a CT based radiomic signature to predict HPV (p16) status, developed in head & neck cancer, in anal and vulvar cancer patients. The patients cohort was composed of 68 anal cancer patients and 7 vulvar cancer patients, with p16 status determined by immunohistochemistry, while a control cohort was composed of 422 lung cancer patients. The patient cohorts come from 4 different centers (Maastro Clinic - the Netherlands, CHU Liege – Belgium, St Luke’s Hospital – Ireland, Cork University Hospital - Ireland). The primary tumor volume was manually delineated for each patient on axial CT images. Prior to analysis, all images were resampled to isotropic voxels of 2 mm, using linear interpolation. A total of 37 radiomics features were calculated from five groups: tumor intensity, shape, texture, Wavelet and Laplacian of Gaussian. The signature was built using regularized logistic regression [1]. The signature was evaluated according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) and the Radiomics Quality Score (RQS). Results: The signature classified anal and vulvar cancers based on their HPV status (positive or negative), with an AUROC of 0.760 comparable to the performance of the original signature developed in oropharyngeal squamous cell carcinomas (AUROC of 0.764) [1]. The model, tested in the control cohort of lung cancer patients, predicted the HPV positive status of 1% of the patients which is in line with expected European prevalence (0 – 10%). This signature is TRIPOD level 4 (57%) with an RQS of 61%. Conclusions: This study supplies an additional insight into HPV imaging phenotype, providing a proof of concept that molecular information can be inferred from standard medical images by means of radiomics. These preliminary but encouraging results may pave the road for further generalization of CT image features of HPV-related tumors and aid in the optimization of future therapy developments [2]. Reference [1] Ralph TH Leijenaar et al., The British Journal of Radiology 2018 91:1086 [2] Immunotherapy Drug with Two Targets Shows Promise against HPV-Related Cancers - accessed on 12/02/2021 - https://www.cancer.gov/

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A prognostic and predictive computational pathology image signature for added benefit of adjuvant chemotherapy in early stage non-small-cell lung cancer

EBioMedicine ◽

10.1016/j.ebiom.2021.103481 ◽

2021 ◽

Vol 69 ◽

pp. 103481

Author(s):

Xiangxue Wang ◽

Kaustav Bera ◽

Cristian Barrera ◽

Yu Zhou ◽

Cheng Lu ◽

...

Keyword(s):

Lung Cancer ◽

Adjuvant Chemotherapy ◽

Small Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Added Benefit ◽

Image Signature ◽

Computational Pathology ◽

Pathology Image

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Human papillomavirus (HPV)-associated early stage non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7560 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7560-7560 ◽

Cited By ~ 3

Author(s):

Rathi Narayana Pillai ◽

Camille Ragin ◽

Gabriel Sica ◽

Madhusmita Behera ◽

Zhengjia Chen ◽

...

Keyword(s):

Lung Cancer ◽

Risk Factor ◽

Early Stage ◽

Smoking Status ◽

Disease Free Survival ◽

Regression Modeling ◽

Parameter Estimates ◽

Early Stage Nsclc ◽

American Patient ◽

Hpv Status

7560 Background: HPV is an established risk factor for cervical and oropharyngeal cancer. It has been suggested as a potential risk factor for lung cancer based on studies conducted mostly in Asian patients with advanced NSCLC. We characterize potential role of HPV in a North American patient population with early stage NSCLC. Methods: We analyzed surgically resected samples of NSCLC patients diagnosed between 2002-2007. HPV status was determined by polymerase chain reaction (PCR) using the INNO-LiPA genotyping Extra Amplification and Genotyping Extra kits, followed by reverse hybridization line probe assay to identify specific HPV serotypes. Differences between HPV+ and HPV- patients were assessed by Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests. Survival was estimated by the Kaplan-Meier method and differences between HPV+ and HPV- patients were assessed by Log-rank test. Multivariable logistic regression modeling was employed to select predictors of HPV+ NSCLC. The significance levels were set at 0.05 for all tests. Results: Paraffin-embedded tumor samples from 208 patients were analyzed; M/F (49%/51%); stage I: 80%; II: 11%; III: 9%; IV: <1%; Caucasians 95.6% and African-Americans (AA) 4.4%. There were 32 (14.9%) HPV+ cases including 10 cases with HPV 16/18. Ethnicity was significantly associated with HPV status (p-value=0.033). AA patients are more likely to be HPV+ (OR: 7.373; p=0.01) and more likely to harbor high risk serotypes 16/18 (OR: 10.8; p=0.05). Regression modeling identified AA ethnicity, adenocarcinoma (ADC) histology and current smoking (parameter estimates of 2.04, -2.34 and -2.82 respectively) as predictors of HPV+ NSCLC. Smoking status and histology showed significant interaction in predicting HPV+ tumors: OR: 0.06; p=0.0023 for smokers with squamous cancer; 2.52; p=0.24 for smokers with ADC and 10.339; p=0.0293 for smokers with adenosquamous cancer. Median disease free survival (NR; p=0.42) and median overall survival (71 months; vs. 55 months) were not significantly different between HPV+ and HPV- patients. Conclusions: HPV positivity is observed in 15% of early stage NSCLC with strong association with AA ethnicity, adenosquamous histology and non-smoking status.

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Comment: predictability of survival in the individual patient with lung cancer

JAMA ◽

10.1001/jama.195.12.1036 ◽

1966 ◽

Vol 195 (12) ◽

pp. 1036-1037 ◽

Cited By ~ 1

Author(s):

P. Rubin

Keyword(s):

Lung Cancer ◽

The Individual

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The question of irradiation therapy in lung cancer

JAMA ◽

10.1001/jama.195.6.471 ◽

1966 ◽

Vol 195 (6) ◽

pp. 471-475 ◽

Cited By ~ 1

Author(s):

M. J. Krant

Keyword(s):

Lung Cancer ◽

Irradiation Therapy

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Video-microscopic measurement of cell-substratum traction forces generated by locomoting keratocytes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146783 ◽

1993 ◽

Vol 51 ◽

pp. 188-189

Author(s):

Tim Oliver ◽

Michelle Leonard ◽

Juliet Lee ◽

Akira Ishihara ◽

Ken Jacobson

Keyword(s):

Silicone Rubber ◽

Molecular Motors ◽

Video Frame ◽

Traction Forces ◽

Cell Traction Forces ◽

Latex Beads ◽

Cell Traction ◽

Local Cell ◽

Microscopic Measurement ◽

Kinetics Of

We are using video-enhanced light microscopy to investigate the pattern and magnitude of forces that fish keratocytes exert on flexible silicone rubber substrata. Our goal is a clearer understanding of the way molecular motors acting through the cytoskeleton co-ordinate their efforts into locomotion at cell velocities up to 1 μm/sec. Cell traction forces were previously observed as wrinkles(Fig.l) in strong silicone rubber films by Harris.(l) These forces are now measureable by two independant means.In the first of these assays, weakly crosslinked films are made, into which latex beads have been embedded.(Fig.2) These films report local cell-mediated traction forces as bead displacements in the plane of the film(Fig.3), which recover when the applied force is released. Calibrated flexible glass microneedles are then used to reproduce the translation of individual beads. We estimate the force required to distort these films to be 0.5 mdyne/μm of bead movement. Video-frame analysis of bead trajectories is providing data on the relative localisation, dissipation and kinetics of traction forces.

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Surgery for Lung Cancer and the Consequences for the Swallow

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp1.sig13.162 ◽

2016 ◽

Vol 1 (13) ◽

pp. 162-168

Author(s):

Pippa Hales ◽

Corinne Mossey-Gaston

Keyword(s):

Lung Cancer ◽

Treatment Options ◽

Vocal Cord Palsy ◽

Subsequent Treatment ◽

Physiological Reserve ◽

Palliative Phase ◽

And Function ◽

The Impact ◽

Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

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