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Article ; Online: National Patterns of Early Adoption of Magnetic Resonance Imaging–Guided Linear Accelerators in 2018 to 2019

James B. Yu, MD, MHS / Connor J. Kinslow, MD / Simon K. Cheng, MD, PhD / Rodney J. Ellis, MD / David P. Horowitz, MD

Advances in Radiation Oncology, Vol 8, Iss 3, Pp 101167- (2023)

2023

Abstract: Purpose: Adaptive magnetic resonance imaging–guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing ... ...

Abstract	Purpose: Adaptive magnetic resonance imaging–guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Methods and Materials: Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 1:1 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White [vs non-White], % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Results: Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. Conclusions: aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of ...
Keywords	Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	616 ; 610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Influenza activity and regional mortality for non-small cell lung cancer

Connor J. Kinslow / Yuankun Wang / Yi Liu / Konstantin M. Zuev / Kunal R. Chaudhary / Tony J. C. Wang / Ciro Donalek / Michael Amori / Simon K. Cheng

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 9

Abstract: Abstract Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in ... ...

Abstract	Abstract Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in patients with cancer remains largely unknown. The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with non-small cell lung cancer (NSCLC) diagnosed between 2009 and 2015. Influenza-like illness (ILI) activity, provided by the Outpatient Influenza-like Illness Surveillance Network of the Center of Disease for Control and Prevention, was merged with the SEER dataset on the state-month level. Regional monthly mortality rates were compared during low versus high flu months in this ecological cohort study. 202,485 patients with NSCLC from 13 SEER-reporting states were included in the analysis. 53 of 1049 state-months (5.1%) had high flu activity. Monthly mortality rates during low and high flu months were 0.041 (95% CI 0.041–0.042) and 0.051 (95% CI 0.050–0.053), respectively (RR 1.24 [95% CI 1.21–1.27]). The association between ILI activity and mortality was observed at the individual state level and in all clinical and regional subgroups. Increased regional influenza activity is associated with higher mortality rates for patients with NSCLC. Vaccine-directed initiatives and increased awareness amongst providers will be necessary to address the growing but potentially preventable burden of influenza-related lung cancer deaths in the U.S.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Smurf2 inhibition enhances chemotherapy and radiation sensitivity in non-small-cell lung cancer

Kunal R. Chaudhary / Connor J. Kinslow / Haiying Cheng / Jose M. Silva / Jiyang Yu / Tony. J. Wang / Tom K. Hei / Balazs Halmos / Simon K. Cheng

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 12

Abstract: Abstract Lung cancer has been the most common cancer worldwide for several decades. The outcomes of patients with locally advanced lung cancer remain dismal, and only a minority of patients survive more than 5 years. However, tumor therapeutic resistance ...

Abstract	Abstract Lung cancer has been the most common cancer worldwide for several decades. The outcomes of patients with locally advanced lung cancer remain dismal, and only a minority of patients survive more than 5 years. However, tumor therapeutic resistance mechanisms are poorly studied. Identification of therapeutic resistance pathways in lung cancer in order to increase the sensitivity of lung tumor cells to therapeutic agents is a crucial but challenging need. To identify novel genes that modulate the response to platinum-based therapy, we performed a genome-wide high-throughput ribonucleic acid interference (RNAi) screen via transfection of human lung cancer (PC9) cells with a viral short hairpin RNA (shRNA) library. We further validated a potential target via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic survival assays on PC9 and A549 lung tumor cells transfected with small interfering RNAs (siRNAs) to successfully downregulate protein expression and then treated with increasing doses of cisplatin or X-ray radiation. We determined protein expression by immunohistochemistry (IHC) after chemoradiotherapy and analyzed gene expression-based survival outcomes in two cohorts of human non-small-cell lung cancer (NSCLC) patients. The screen identified several targets involved in epithelial-to-mesenchymal transition (EMT), including Smurf1, Smurf2, YAP1, and CEBPZ, and glycolytic pathway proteins, including PFKFB3. Furthermore, we found that the small molecule proteasome inhibitor bortezomib significantly downregulated Smurf2 in lung cancer cells. The addition of bortezomib in combination with cisplatin and radiation therapy in PC9 and A549 cells led to an increase in deoxyribonucleic acid (DNA) double-strand breaks with increased numbers of γ-H2AX-positive cells and upregulation of apoptosis. Finally, we found that Smurf2 protein expression was upregulated in situ after treatment with cisplatin and radiation therapy in a relevant cohort of patients with stage III NSCLC. ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clear Cell Adenocarcinoma of the Urinary Bladder Is a Glycogen-Rich Tumor with Poorer Prognosis

Zhengqiu Zhou / Connor J. Kinslow / Peng Wang / Bin Huang / Simon K. Cheng / Israel Deutsch / Matthew S. Gentry / Ramon C. Sun

Journal of Clinical Medicine, Vol 9, Iss 1, p

2020 Volume 138

Abstract: Clear cell adenocarcinoma (CCA) is a rare variant of urinary bladder carcinoma with a glycogen-rich phenotype and unknown prognosis. Using the National Cancer Institute’s surveillance, epidemiology, and end results (SEER) program database, we documented ... ...

Abstract	Clear cell adenocarcinoma (CCA) is a rare variant of urinary bladder carcinoma with a glycogen-rich phenotype and unknown prognosis. Using the National Cancer Institute’s surveillance, epidemiology, and end results (SEER) program database, we documented recent trends in incidence, mortality, demographical characteristics, and survival on this rare subtype of urinary bladder cancer. The overall age-adjusted incidence and mortality of CCA was 0.087 (95% confidence interval (CI): 0.069−0.107) and 0.064 (95% CI: 0.049−0.081) respectively per million population. In comparison to non-CCAs, CCAs were more commonly associated with younger age (<60 years old, p = 0.005), female ( p < 0.001), black ethnicity ( p = 0.001), grade III ( p < 0.001), and higher AJCC 6th staging ( p < 0.001). In addition, CCA patients more frequently received complete cystectomy ( p < 0.001) and beam radiation ( p < 0.001) than non-CCA patients. Our study showed a poorer prognosis of CCAs compared to all other carcinomas of the urinary bladder ( p < 0.001), accounted for by higher tumor staging of CCA cases. This study adds to the growing evidence that glycogen-rich cancers may have unique characteristics affecting tumor aggressiveness and patient prognosis. Additional mechanistic studies are needed to assess whether it’s the excess glycogen that contributes to the higher stage at diagnosis.
Keywords	glycogen ; clear-cell adenocarcinoma ; urinary bladder ; seer program database ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients.

Samuel P Heilbroner / Eric P Xanthopoulos / Donna Buono / Daniel Carrier / Ben Y Durkee / Michael Corradetti / Tony J C Wang / Alfred I Neugut / Dawn L Hershman / Simon K Cheng

PLoS ONE, Vol 16, Iss 5, p e

2021 Volume 0252053

Abstract: Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years ...

Abstract	Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86-1.09), ETFS (HR 1.05; 95% CI 0.93-1.18), CSS (HR 0.94; 95% CI 0.84-1.04), or OS (HR 0.95; 95% CI 0.87-1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Features, Survival and Prognostic Factors of Glycogen-Rich Clear Cell Carcinoma (GRCC) of the Breast in the U.S. Population

Zhengqiu Zhou / Connor J. Kinslow / Hanina Hibshoosh / Hua Guo / Simon K. Cheng / Chunyan He / Matthew S. Gentry / Ramon C. Sun

Journal of Clinical Medicine, Vol 8, Iss 2, p

2019 Volume 246

Abstract: The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical ... ...

Abstract	The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast carcinomas. We demonstrate that GRCC is more likely to be identified as high grade, advanced stage, and more likely to have triple negative receptor status. GRCC cases display a poorer prognosis than non-GRCC carcinomas of the breast irrespective of age, AJCC staging, tumor grade, joint hormone receptor/human epidermal growth factor receptor 2 (HER2) status, and treatment. Similar to non-GRCC carcinomas, older age and higher American Joint Committee on Cancer (AJCC)/TNM staging were associated with poorer prognosis for GRCC, while treatment with surgery and radiation were associated with improved survival. Radiation, specifically in the setting of breast-conserving surgery, further improved survival compared to surgery alone. Our study highlights the poorer prognosis associated with glycogen accumulation in breast cancers and hence stresses the importance of identifying this more aggressive tumor type.
Keywords	glycogen ; breast cancer ; SEER program database ; clear cell carcinoma ; prognosis ; survival ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of β-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Kunal R. Chaudhary / Sherry X. Yan / Samuel P. Heilbroner / Joshua R. Sonett / Mark B. Stoopler / Catherine Shu / Balazs Halmos / Tony J.C. Wang / Tom K. Hei / Simon K. Cheng

Journal of Clinical Medicine, Vol 8, Iss 5, p

2019 Volume 575

Abstract: Introduction: Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies that suggest stimulation of β-adrenergic receptors (β-AR) promotes tumor invasion and ... ...

Abstract	Introduction: Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies that suggest stimulation of β-adrenergic receptors (β-AR) promotes tumor invasion and therapy resistance. We investigated whether β-AR inhibition with beta-blockers acts as a chemotherapy and radiation sensitizer in vitro and in patients treated with chemoradiation for locally advanced NSCLC. Methods: We investigated the effects of the non-selective beta-blocker propranolol on two human lung adenocarcinoma cell lines (PC9, A549) treated with radiation or cisplatin. We retrospectively evaluated 77 patients with Stage IIIA NSCLC who received induction chemoradiation followed by surgery. Pathological and imaging response, metastatic rate, and survival were analyzed using SPSS v22.0 and PrismGraphpad6. Results: Propranolol combined with radiation or cisplatin decreased clonogenic survival of PC9 and A549 cells in vitro ( p < 0.05). Furthermore, propranolol decreased expression of phospho-protein kinase A (p-PKA), a β-adrenergic pathway downstream activation target, in both cell lines compared to irradiation or cisplatin alone ( p < 0.05). In patients treated for Stage IIIA NSCLC, 16 took beta-blockers, and 61 did not. Beta-blockade is associated with a trend to improved overall survival (OS) at 1 year (81.3% vs 57.4%, p = 0.08) and distant metastasis-free survival (DMFS) (2.6 years vs. 1.3 years, p = 0.16). Although beta-blocker use was associated with decreased distant metastases (risk ratio (RR) 0.19; p = 0.03), it did not affect primary tumor pathological response ( p = 0.40) or imaging response ( p = 0.36). Conclusions: β-AR blockade enhanced radiation and cisplatin sensitivity of human lung cancer cells in vitro. Use of beta-blockers is associated with decreased distant metastases and potentially improved OS and DMFS. Additional studies are warranted to evaluate the role of beta-blockers as a chemoradiation sensitizer in locally advanced ...
Keywords	beta-blocker ; repurposed drugs ; chemotherapy ; radiation ; sensitivity ; non-small cell lung cancer ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors.

Simon K Cheng / Felix Olale / Ali H Brivanlou / Alexander F Schier

PLoS Biology, Vol 2, Iss 2, p E

2004 Volume 30

Abstract: Members of the EGF-CFC family play essential roles in embryonic development and have been implicated in tumorigenesis. The TGFbeta signals Nodal and Vg1/GDF1, but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We report that the ... ...

Abstract	Members of the EGF-CFC family play essential roles in embryonic development and have been implicated in tumorigenesis. The TGFbeta signals Nodal and Vg1/GDF1, but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We report that the TGFbeta signaling antagonist Lefty also acts through an EGF-CFC-dependent mechanism. Lefty inhibits Nodal and Vg1 signaling, but not Activin signaling. Lefty genetically interacts with EGF-CFC proteins and competes with Nodal for binding to these coreceptors. Chimeras between Activin and Nodal or Vg1 identify a 14 amino acid region that confers independence from EGF-CFC coreceptors and resistance to Lefty. These results indicate that coreceptors are targets for both TGFbeta agonists and antagonists and suggest that subtle sequence variations in TGFbeta signals result in greater ligand diversity.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2004-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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