Publications by authors named "Biwei Cao"

14 Publications

  • Page 1 of 1

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas following Chimeric Antigen Receptor (CAR) T-Cell Therapy.

Int J Radiat Oncol Biol Phys 2021 Jul 6. Epub 2021 Jul 6.

Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.

Purpose: Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, the majority of treated patients relapse. Patterns of failure following CAR T have not been previously characterized and may provide insights into the mechanisms of resistance guiding future treatment strategies.

Methods And Materials: Retrospective analysis of R/R large B-cell lymphoma patients treated with anti-CD19 CAR T at an NCI-designated Comprehensive Cancer Center from 2015 to 2019. Pre- and post-treatment PET/CTs were analyzed to assess the progression of existing (local failures) versus new, non-overlapping lesions (de novo failures) and to identify lesions at high-risk for progression.

Results: A total of 469 pretreatment lesions in 63 patients were identified. At a median follow-up of 12•6 months, 36 (57%) patients recurred. The majority (n=31, 86%) had a component of local failure with 13 (36%) patients exhibiting strictly local failures. Even at progression, 84% of recurrent patients continued to have a subset of pretreatment lesions maintain PET/CT resolution. Lesions at high-risk for local failure included those with a diameter ≥5cm (OR 2•34, 95%CI 1•55-3•55; p<0•001), an SUV≥10 (OR 2•08, 95%CI 1•38-3•12; p<0•001), or that were extranodal (OR 1.49, 95% CI 1.10-2.04; p=0.01). In the 69 patients eligible for survival analysis, those with any lesion ≥5cm (n=46, 67%) experienced inferior PFS (HR 2•41, 95%CI 1•15-5•04; p=0•02) and OS (HR 3•36, 95%CI 1•17-9•96; p=0•02).

Conclusion: The majority of patients who recur following CAR T experience a component of local progression. Furthermore, lesions with high-risk features, particularly large size, were associated with inferior treatment efficacy and patient survival. Taken together, these observations suggest that lesion-specific resistance may contribute to CAR T treatment failure. Locally-directed therapies to high-risk lesions, such as radiotherapy, may be a viable strategy to prevent CAR T failures in select patients.
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http://dx.doi.org/10.1016/j.ijrobp.2021.06.038DOI Listing
July 2021

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma.

Blood 2021 May;137(19):2621-2633

Department of Blood and Marrow Transplant and Cellular Immunotherapy.

Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death-ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.
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http://dx.doi.org/10.1182/blood.2020007445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120145PMC
May 2021

Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers.

Cancer 2021 Apr 8;127(8):1293-1300. Epub 2020 Dec 8.

Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida.

Background: Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored.

Methods: Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling.

Results: Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19).

Conclusions: The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered.

Lay Summary: The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.
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http://dx.doi.org/10.1002/cncr.33364DOI Listing
April 2021

Characteristic of Clinical Studies on Baduanjin during 2000-2019: A Comprehensive Review.

Evid Based Complement Alternat Med 2020 16;2020:4783915. Epub 2020 Oct 16.

Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China.

To date, a growing number of clinical studies have demonstrated the safety and health benefits from Baduanjin intervention. Based on this, our objective is to systematically retrieve and summarize the clinical studies on Baduanjin, with a view to providing more evidence-based evidence in support of the application of Baduanjin for healthcare, and to identify the shortcomings of existing research and provide feasibility suggest for further clinical research. Both four English language and four Chinese language electronic databases were used to search articles related to Baduanjin during 2000-2019. SPSS 22.0 software was used to analyze the data, and the risk of bias tool in the RevMan 5.3.5 software was used to evaluate the methodological quality of randomized controlled trials. A total of 810 publications were identified, including 43 (5.3%) systematic reviews, 614 (75.8%) randomized controlled trials, 66 (8.1%) nonrandomized controlled clinical studies, 84 (10.4%) case series, and 3 (0.4%) case reports. The top 10 diseases/conditions included diabetes, chronic obstructive pulmonary disease, hypertension, low back pain, neck pain, stroke, coronary heart disease, cognitive impairment, insomnia, and osteoporosis or osteopenia. The style of State General Administration of Sport of China in 2003 was the most commonly used version of Baduanjin, and Baduanjin was practiced with an average of 35 minutes, 1 or 2 times a day, 3-5 days per week, and a 18-week average duration. It is also worth noting that there were no serious adverse events related to Baduanjin intervention. Most studies were small sample size research, and the methodological quality of randomized controlled trials is generally low. The clinical studies of Baduanjin have a substantial quantity and evidence base. However, there are significant differences among different studies in the specific intervention measures such as style, intensity, duration, learning, and practice methods, which need to be further standardized and unified. Further high-quality designed and reporting studies are recommended to further validate the clinical benefits of Baduanjin.
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http://dx.doi.org/10.1155/2020/4783915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603575PMC
October 2020

Reply By Authors.

J Urol 2021 01 23;205(1):108. Epub 2020 Oct 23.

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

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http://dx.doi.org/10.1097/JU.0000000000001325.03DOI Listing
January 2021

Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy.

J Urol 2021 Jan 12;205(1):100-108. Epub 2020 Aug 12.

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Purpose: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone.

Materials And Methods: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival.

Results: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy.

Conclusions: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.
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http://dx.doi.org/10.1097/JU.0000000000001325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864376PMC
January 2021

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer.

Oncologist 2020 12 14;25(12):e1893-e1899. Epub 2020 Sep 14.

Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida, USA.

Lessons Learned: The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy. Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily. The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

Background: The RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.

Methods: This was a phase I study with a 3+3 design in patients with treatment-naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.

Results: A total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose-limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment-related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression-free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated-ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated-ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.

Conclusion: Trametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.
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http://dx.doi.org/10.1634/theoncologist.2020-0759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186409PMC
December 2020

Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Clin Cancer Res 2020 09 15;26(18):4823-4831. Epub 2020 Jul 15.

Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).

Experimental Design: Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.

Results: We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.

Conclusions: These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501265PMC
September 2020

PDXGEM: patient-derived tumor xenograft-based gene expression model for predicting clinical response to anticancer therapy in cancer patients.

BMC Bioinformatics 2020 Jul 6;21(1):288. Epub 2020 Jul 6.

Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, 33620, USA.

Background: Cancer is a highly heterogeneous disease with varying responses to anti-cancer drugs. Although several attempts have been made to predict the anti-cancer therapeutic responses, there remains a great need to develop highly accurate prediction models of response to the anti-cancer drugs for clinical applications toward a personalized medicine. Patient derived xenografts (PDXs) are preclinical cancer models in which the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. In the present study, we develop a bioinformatics analysis pipeline to build a predictive gene expression model (GEM) for cancer patients' drug responses based on gene expression and drug activity data from PDX models.

Results: Drug sensitivity biomarkers were identified by performing an association analysis between gene expression levels and post-treatment tumor volume changes in PDX models. We built a drug response prediction model (called PDXGEM) in a random-forest algorithm by using a subset of the drug sensitvity biomarkers with concordant co-expression patterns between the PDXs and pretreatment cancer patient tumors. We applied the PDXGEM to several cytotoxic chemotherapies as well as targeted therapy agents that are used to treat breast cancer, pancreatic cancer, colorectal cancer, or non-small cell lung cancer. Significantly accurate predictions of PDXGEM for pathological response or survival outcomes were observed in extensive independent validations on multiple cancer patient datasets obtained from retrospective observational studies and prospective clinical trials.

Conclusion: Our results demonstrated the strong potential of using molecular profiles and drug activity data of PDX tumors in developing a clinically translatable predictive cancer biomarkers for cancer patients. The PDXGEM web application is publicly available at http://pdxgem.moffitt.org .
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http://dx.doi.org/10.1186/s12859-020-03633-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336455PMC
July 2020

Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma.

Haematologica 2021 04 1;106(4):978-986. Epub 2021 Apr 1.

Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA.

CD19 CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with >= grade 3 neutropenia seen in 21/70 (30-0%) patients at day 30 and persisting in 3/31 (9-7%) patients at 1 year. B cells were undetectable in 30/34 (88-2%) patients at day 30, but were detected in 11/19 (57-9%) at 1 year. Median IgG levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/μl at 1 year after axi-cel (n=19, range 33 - 269). In total, 23/85 (27-1%) patients received IVIG after axi-cel, and 34/85 (40-0%) received G-CSF. Infections in the first 30 days occurred in 31/85 (36-5%) patients, of which 11/85 (12-9%) required intravenous antibiotics or hospitalization ("severe") and were associated with cytokine release syndrome (CRS), neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, 7 severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T cell immunosuppression without severe infection.
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http://dx.doi.org/10.3324/haematol.2019.238634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017820PMC
April 2021

Long noncoding RNA, , as a prognostic biomarker in head and neck squamous cell carcinoma (HNSCC).

Am J Transl Res 2020 15;12(2):684-696. Epub 2020 Feb 15.

Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center Tampa, FL, USA.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy characterized by frequent mutations and metastasis. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis and serve as novel prognostic biomarkers in different cancers. To enhance our understanding of lncRNAs that may have biological significance in HNSCC and may serve as prognostic biomarkers, we globally profiled lncRNAs in HNSCC by analyzing the RNA-seq data from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. Of 3576 lncRNAs, we identified 926 (higher-688, lower-238) lncRNAs with a 2-fold abundance difference among the forty HNSCC and paired adjacent normal tissue. We investigated differential abundance of lncRNAs based on mutation and p16 status. We found 133 lncRNAs to have differential abundance by 2-fold among the mutant vs wild-type samples, whereas among p16-negative vs positive samples, we identified 710 lncRNAs with the same criteria. Meanwhile, analysis of the 15 most abundant lncRNAs in the tumor samples identified five lncRNAs whose higher abundance was associated with poor overall patient survival. Among these five, higher abundance of associated with poor patient survival in an independent cohort of 82 HNSCC patients. To further evaluate the potential function of , we performed lncRNA-mRNAs co-expression analysis and found that higher abundance of associated with cancer-related biological pathways including EMT and other inflammatory response pathways. In summary, we report is more abundant in tumors compared to adjacent normal tissue and that it may serve as a potential prognostic biomarker in HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061833PMC
February 2020

Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy.

Front Immunol 2020 25;11:164. Epub 2020 Feb 25.

Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.

Phenotyping of immune cell subsets in clinical trials is limited to well-defined phenotypes, due to technological limitations of reporting flow cytometry multi-dimensional phenotyping data. We developed a multi-dimensional phenotyping analysis tool and applied it to detect nitric oxide (NO) levels in peripheral blood immune cells before and after adjuvant ipilimumab co-administration with a peptide vaccine in melanoma patients. We analyzed inhibitory and stimulatory markers for immune cell phenotypes that were felt to be important in the NO analysis. The pipeline allows visualization of immune cell phenotypes without knowledge of clustering techniques and to categorize cells by association with relapse-free survival (RFS). Using this analysis, we uncovered the potential for a dichotomous role of NO as a pro- and anti-melanoma factor. NO was found in subsets of immune-suppressor cells associated with shorter-term (≤ 1 year) RFS, whereas NO was also present in immune-stimulatory effector cells obtained from patients with significant longer-term (> 1 year) RFS. These studies provide insights into the cell-specific immunomodulatory role of NO. The methods presented herein can be applied to monitor the pro- and anti-tumor effects of a variety of immune-based therapeutics in cancer patients. NCT00084656 (https://clinicaltrials.gov/ct2/show/NCT00084656).
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http://dx.doi.org/10.3389/fimmu.2020.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052497PMC
March 2021

Corrigendum to "multi-resolution classification of exhaled aerosol images to detect obstructive lung diseases in small airways" [comput. Biol. Med. 87 (2017) 57-69].

Comput Biol Med 2019 Nov 13;114:103443. Epub 2019 Sep 13.

The Rutgers Center for Computational and Integrative Biology, Camden, NJ, 08102, USA.

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http://dx.doi.org/10.1016/j.compbiomed.2019.103443DOI Listing
November 2019

Multi-resolution classification of exhaled aerosol images to detect obstructive lung diseases in small airways.

Comput Biol Med 2017 08 20;87:57-69. Epub 2017 May 20.

The Rutgers Center for Computational and Integrative Biology, Camden, NJ, 08102, USA.

Exhaled aerosol patterns have been used to detect obstructive respiratory diseases in the upper airways. Signals from small airway diseases are weak and may not manifest themselves in the exhaled aerosol patterns. Therefore, it will be more challenging to detect abnormalities in small airways. The objective of this study is to develop a simulation-based classification model that can accurately classify small airway diseases. The model performance was evaluated in five obstructed models that are located in lung bifurcations G7-9. The exhaled aerosol images were quantified using local fractal dimensions at different sampling resolutions (n × n). The datasets were classified using both the random forest (RF) and support vector machine (SVM) algorithms. Results show that RF performs slightly and persistently better than SVM. The sampling resolution of 12 × 12 gave the optimal classification for both algorithms. Based on the lung models with predefined obstructive levels, the optimal classification accuracy is 87.0% for 5-class classification, and is 92.5% for 4-class classification by regrouping the mislabeled samples. The proposed model with multi-resolution fractal feature extraction and RF algorithm appears to be sensitive enough to accurately distinguish airway abnormalities in small airways beyond G7 with healthy bronchiole diameter <4 mm. This aerosol-based breath test is promising to develop into an alternative or supplemental tool to the low-dose CT scanning for lung cancer screening.
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http://dx.doi.org/10.1016/j.compbiomed.2017.05.019DOI Listing
August 2017
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