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

Abstract

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.

The Fractal and GLCM Textural Parameters of Chromatin May Be Potential Biomarkers of Papillary Thyroid Carcinoma in Hashimoto's Thyroiditis Specimens

“…In this study, the quantification of the differences between the studied samples was verified for the first time using the FD, lacunarity, and several GLCM textural parameters of the follicular cell nuclei. In contrast with many earlier findings, which have demonstrated a higher chromatin FD in various tumor tissues (Sedivy et al, 1999;Dey & Mohanty, 2003;Mashiah et al, 2008;Bedin et al, 2010;Ferro et al, 2011;Huang et al, 2012;Jabalee et al, 2018;Mambetsariev et al, 2019;Metze et al, 2019), the results of our current study showed a lower chromatin FD in tumor tissues than in the corresponding benign tissues. Chromatin is divided into two distinct regions based on the gene density: (i) euchromatin (uncondensed and gene-rich conformation) and (ii) heterochromatin (condensed and gene-poor conformation).…”

“…Quantitative morphologic interpretation of the stained histologic sections or cytologic preparations may be done by basic morphometry and sophisticated texture analysis based on digitalized images (Ferreira et al, 2006; Metze et al, 2009, 2019; Metze, 2013). Among these medical image analyses, the fractal and GLCM textural analyses have shown to be of increasing importance particularly for the investigation of various tumor types (Sedivy et al, 1999; Dey & Mohanty, 2003; Mashiah et al, 2008; Bedin et al, 2010; Ferro et al, 2011; Huang et al, 2012; Jabalee et al, 2018; Mambetsariev et al, 2019). It is well known that HT and PTC specimens sporadically share the same morphological features, immunohistochemical staining, and molecular profiles (Arif et al, 2002; Weetman, 2004; Rhoden et al, 2006; Ohmori et al, 2007; Anand et al, 2014); therefore, the differential diagnosis between the HT-alone and the HT-associated PTC specimens is not always easy, even for a trained observer.…”

“…morphometry and sophisticated texture analysis based on digitalized images (Ferreira et al, 2006;Metze et al, 2009Metze et al, , 2019Metze, 2013). Among these medical image analyses, the fractal and GLCM textural analyses have shown to be of increasing importance particularly for the investigation of various tumor types (Sedivy et al, 1999;Dey & Mohanty, 2003;Mashiah et al, 2008;Bedin et al, 2010;Ferro et al, 2011;Huang et al, 2012;Jabalee et al, 2018;Mambetsariev et al, 2019). It is well known that HT and PTC specimens sporadically share the same morphological features, immunohistochemical staining, and molecular Sum Entropy for 1 px (d), 4 px (e), and 8 px (f) and Difference Entropy for 1 px (g), 4 px (h), and 8 px (i).…”

Role of fractal analysis in detection of dysplasia in potentially malignant disorders

“…[ 18 ] reviewed the role fractal dimension and found that FD increases in carcinogenesis. In addition, FD has been used for the classification of breast tumors,[ 19 ] in therapeutic response of small cell lung cancer[ 20 ] and to differentiate benign and malignant thyroid nodule. [ 15 ]…”

New Clinical Applications-sintilimab Combined with Albumin-bound Paclitaxel/cisplatin in Treatment of Relapsed or Refractory ES-SCLC

“…The prognosis of patients is extremely poor and the mortality rate is very high. About two-thirds of SCLC patients are diagnosed at the extensive stage (ES) [3], and the median survival time of ES-SCLC patients is about 9.4-12.8 months, and the survival rate is between 5.2%-19.5% [4,5]. However, almost all patients will suffer recurrence and metastasis within 1-2 years after standard first-line treatment.…”