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J Clin Med. 2019 Jul 16;8(7). pii: E1038. doi: 10.3390/jcm8071038.

Small Cell Lung Cancer Therapeutic Responses Through Fractal Measurements: From Radiology to Mitochondrial Biology.

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City of Hope, Dept. of Medical Oncology and Therapeutics Research, Duarte, CA 91010, USA.
Abbott Molecular, Des Plaines, IL 60018, USA.
Center for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
City of Hope, Center for Informatics, Duarte, CA 91010, USA.
City of Hope, Dept. of Computational & Quantitative Medicine, Duarte, CA 91010, USA.
University of Nebraska Medical Center, Dept. of Biochemistry and Molecular Biology, Omaha, NE 68198, USA.
City of Hope, Dept. of Diagnostic Radiology, Duarte, CA 91010, USA.
City of Hope, Dept. of Medical Oncology and Therapeutics Research, Duarte, CA 91010, USA.


Small cell lung cancer (SCLC) is an aggressive neuroendocrine disease with an overall 5 year survival rate of ~7%. Although patients tend to respond initially to therapy, therapy-resistant disease inevitably emerges. Unfortunately, there are no validated biomarkers for early-stage SCLC to aid in early detection. Here, we used readouts of lesion image characteristics and cancer morphology that were based on fractal geometry, namely fractal dimension (FD) and lacunarity (LC), as novel biomarkers for SCLC. Scanned tumors of patients before treatment had a high FD and a low LC compared to post treatment, and this effect was reversed after treatment, suggesting that these measurements reflect the initial conditions of the tumor, its growth rate, and the condition of the lung. Fractal analysis of mitochondrial morphology showed that cisplatin-treated cells showed a discernibly decreased LC and an increased FD, as compared with control. However, treatment with mdivi-1, the small molecule that attenuates mitochondrial division, was associated with an increase in FD as compared with control. These data correlated well with the altered metabolic functions of the mitochondria in the diseased state, suggesting that morphological changes in the mitochondria predicate the tumor's future ability for mitogenesis and motogenesis, which was also observed on the CT scan images. Taken together, FD and LC present ideal tools to differentiate normal tissue from malignant SCLC tissue as a potential diagnostic biomarker for SCLC.


fractal dimension; lacunarity; mitochondria; radiology; small cell lung cancer

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