107 results on '"Rami Manochakian"'
Search Results
2. Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis
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Blake J. McKinley, Tanmayi S. Pai, Emily B. Wolf, Shenduo Li, Guilherme Sacchi de Camargo Correia, Yujie Zhao, Rami Manochakian, and Yanyan Lou
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NSCLC ,early discontinuation ,progression-free survival ,overall survival ,stage IV ,metastatic ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionLimited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs).MethodsWe conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis.ResultsA total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1–2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI.ConclusionsPatients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.
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- 2024
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3. Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy
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Shenduo Li, Rami Manochakian, Ruqin Chen, Jaydeepbhai Patel, Jyothik Varun Inampudi, Koshiya R. Hiren, Yujie Zhao, and Yanyan Lou
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NSCLC ,immunotherapy ,atezolizumab ,docetaxel ,ramucirumab ,PD-1/L1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundAtezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy were excluded from these trials. The standard of care second-line therapy for these patients remains to be docetaxel with or without ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in immunotherapy-pretreated patients are unknown.MethodsWe conducted a retrospective study of all patients with locally advanced or metastatic NSCLC who were pretreated with immunotherapy at Mayo Clinic Jacksonville and Rochester from 2016 to 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included.ResultsIn this cohort of 165 patients, 12.7% (n=21), 49.1% (n=81), and 38.2% (n=63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. 1-year landmark progression-free survival (PFS) were 23.8%, 6.2%, and 3.2% (p=0.006), and 2-year landmark PFS were 14.3%, 0%, and 0% (p
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- 2024
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4. The role of immunotherapy sensitizers and novel immunotherapy modalities in the treatment of cancer
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Guilherme Sacchi de Camargo Correia, Yujie Zhao, Rami Manochakian, and Yanyan Lou
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immunotherapy ,immune checkpoint inhibitors ,immunotherapy sensitizer ,tumor microenvironment ,cancer immunology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The importance of the immune system in the response against cancer has always been a subject of intense investigation. The advent of immune checkpoint inhibitors has transformed the landscape of oncologic treatments, while expanding the understanding of this disease’s pathophysiology. Consequently, many therapies are being investigated, with interventions directed at different steps and pathways of the immune response. Relevantly, immunotherapy sensitizers have arisen as approaches focused on the synergistic effects of immunotherapy combination, or the combination of immunotherapy and other treatment modalities, such as chemotherapy or radiation therapy. Concomitantly, novel immunotherapy modalities are also in development. Approaches focusing from the tumor intrinsic pathways to the tumor microenvironment and ex-vivo interventions, such as CAR-T cell therapies and tumor-infiltrating lymphocytes are important examples. Although many of those interventions were initially envisioned as standalone options, their combination has demonstrated promising results in early-phase in vitro studies and clinical trials. The possibility of coupling different immunotherapy modalities, as well as with other techniques, further strengthen the concept of sensitizers, allowing for deeper and more robust responses in cancer treatment. This review aims to present an overview of the concepts of these sensitizing mechanisms that are the basis for the synergistic effects of immunotherapy combination, or the combination of immunotherapy and a multitude of therapeutic strategies. Novel immunotherapy modalities are also presented, focusing on the potential of combining them with sensitizer interventions. Understanding the complexity underlying these principles may be the key for future breakthroughs and improved patient outcomes.
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- 2024
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5. A Case of Full Recovery from Prolonged Cardiac Arrest after Infusion with Paclitaxel and Pembrolizumab
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Omar Sh Ahmed, Himil Mahadevia, Rami Manochakian, Yujie Zhao, Manisha Salinas, Andras Khoor, Jordan LeGout, and Yanyan Lou
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cardiotoxicity ,immunotherapy ,chemotherapy ,lung cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Lung cancer is one of the most common cancers and has the highest risk of mortality in both genders. This devastating cancer is also a significant financial and emotional burden to patients and the healthcare system. Chemotherapy and immunotherapy have become the cornerstone for the treatment of lung cancer. However, treatment may come with severe and sometimes fatal side effects. In this report, we present the case of a 52-year-old Caucasian male who suffered two episodes of prolonged cardiac arrest after the infusion of paclitaxel and pembrolizumab.
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- 2022
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6. Trends in participant race and sex reporting in lung cancer phase III clinical trials
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Faaiq N. Aslam, Rami Manochakian, Yanyan Lou, Gerardo Colon‐Otero, and Taimur Sher
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clinical trials ,disparities ,lung cancer ,NIH Revitalization Act ,race ,sex ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Clinical trials are an essential part of advancing care for cancer patients. Historically, however, racial minorities and females have been underrepresented in these trials. Efforts like the National Institute of Health Revitalization Act attempted to mitigate these disparities, but despite these efforts, they continue to exist. These disparities can subsequently lead to minorities and females receiving suboptimal care. Aims The purpose of our study was to understand the changing trends in reporting of participant race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years given these consequences of poor representation. Methods and results A total of 426 articles reporting the results of phase III lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. From these articles, data on participant sex and race were collected from the demographic tables to construct the database for this study. This database was subsequently used to determine the rate of reporting of demographic factors like race and sex and the participation trends over the time of minority and female participation in lung cancer phase III clinical trials. The SciPy Stats package for Python was used to calculate descriptive statistics, 95% confidence intervals, two sample t‐test, one‐way analysis of variance test, and Pearson's correlation coefficients. The Matplotlib package for Python was used for figure generation. Only 137 (32.2%) of the 426 studies analyzed reported the race of participants. Among those studies, we found that the mean participation rate of White participants was significantly higher (82.65%; p
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- 2023
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7. Brief report: risk stratification following curative therapy for stage I NSCLC
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Emily Butts, Denise Gococo-Benore, Tanmayi Pai, Muhamad Alhaj Moustafa, Fei Heng, Ruqin Chen, Yujie Zhao, Rami Manochakian, and Yanyan Lou
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resection ,surveillance ,recurrence ,second primary lung cancer ,imaging ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionSurveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy.MethodsWe identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence.ResultsNegative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007).ConclusionsAn individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.
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- 2023
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8. First Report of Management of Sequential Small Cell Transformation and ALK I1171T Mutation as Resistance Mechanisms in a Patient With ALK-EML4 Fused Non–Small Cell Lung Adenocarcinoma With a Novel Combination of Temozolomide and Lorlatinib: A Case Report
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Umair Majeed, MD, Shenduo Li, MD, PhD, Karan Seegobin, MBBS, Aziza Nassar, MD, Rami Manochakian, MD, Yujie Zhao, MD, PhD, and Yanyan Lou, MD, PhD
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Case report ,ALK-EML4 ,ALK-positive NSCLC ,Small cell transformation ,ALK I1171T mutation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ALK-EML4 fusion-positive lung adenocarcinomas (LUADs) are effectively treated with ALK tyrosine kinase inhibitors, but most patients eventually develop resistance to these drugs owing to ALK-dependent or independent mechanisms. Endothelial to mesenchymal transformation with SCLC development is an ALK-independent mechanism of resistance that has not been previously reported with sequential ALK I1171T mutation while the patient is on treatment for the SCLC. Here, we report the first case of sequential SCLC transformation followed by ALK I1171T mutation in a patient with ALK-EML4 fusion-positive LUAD. After progression on multiple lines of therapy, we describe our experience of managing ALK-mutant LUAD and transformed SCLC with a novel combination of lorlatinib and temozolomide. We also briefly summarize cases of endothelial to mesenchymal transformation ALK-mutant LUAD from the literature.
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- 2023
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9. Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report
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Aakash Desai, Sagar Rakshit, Radhika Bansal, Yash Ashara, Ashley Potter, Rami Manochakian, Yanyan Lou, Yujie Zhao, Vinicius Ernani, Panos Savvides, Anna Schwecke, Nicole Moffett, Craig Hocum, Konstantinos Leventakos, Alex Adjei, Randolph Marks, Julian Molina, Aaron S. Mansfield, Zong-Ming Chen, and Anastasios Dimou
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Immunotherapy ,Sotorasib ,Hepatotoxicity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC. Methods: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022. Results: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27–123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients.Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4–542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31–90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively. Conclusion: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.
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- 2023
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10. Genomic landscape of lung adenocarcinomas in different races
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Huashan Shi, Karan Seegobin, Fei Heng, Kexun Zhou, Ruqin Chen, Hong Qin, Rami Manochakian, Yujie Zhao, and Yanyan Lou
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genomic ,lung adenocarcinomas ,races ,target therapy ,disparities ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundLung adenocarcinoma is a molecularly heterogeneous disease. Several studies, including The Cancer Genome Atlas Research Network (TCGA) and Lung Cancer Mutation Consortium (LCMC), explored the genetic alterations among different ethnic groups. However, minority groups are often under-represented in these relevant studies and the genomic alterations among racial groups are not fully understood.MethodsWe analyze genomic characteristics among racial groups to understand the diversities and their impact on clinical outcomes.ResultsNative Americans had significantly higher rates of insertions and deletions than other races (P
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- 2022
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11. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends
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Umair Majeed, Rami Manochakian, Yujie Zhao, and Yanyan Lou
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Advanced NSCLC ,Targeted therapy ,Phase I/II clinical trials ,First-in-human ,Lung cancer ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Lung cancer remains the leading cause of cancer-related mortality in both men and women in the US and worldwide. Non-small cell lung cancer is the most common variety accounting for 84% of the cases. For a subset of patients with actionable mutations, targeted therapy continues to provide durable responses. Advances in molecular and immunohistochemical techniques have made it possible to usher lung cancer into the era of personalized medicine, with the patient getting individualized treatment based on these markers. This review summarizes the recent advances in advanced NSCLC targeted therapy, focusing on first-in-human and early phase I/II clinical trials in patients with advanced disease. We have divided our discussion into different topics based on these agents' mechanisms of action. This article is aimed to be the most current review of available and upcoming targeted NSCLC treatment options. We will also summarize the currently available phase I/II clinical trial for NSCLC patients at the end of each section.
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- 2021
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12. Immunotherapies targeting stimulatory pathways and beyond
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Julian A. Marin-Acevedo, ErinMarie O. Kimbrough, Rami Manochakian, Yujie Zhao, and Yanyan Lou
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Cancer ,Immunotherapy ,Tumor microenvironment ,Immune evasion ,Cytotoxic T lymphocytes ,Immune checkpoint ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Co-stimulatory and co-inhibitory molecules play a critical role in T cell function. Tumor cells escape immune surveillance by promoting immunosuppression. Immunotherapy targeting inhibitory molecules like anti-CTLA-4 and anti-PD-1/PD-L1 were developed to overcome these immunosuppressive effects. These agents have demonstrated remarkable, durable responses in a small subset of patients. The other mechanisms for enhancing anti-tumor activities are to target the stimulatory pathways that are expressed on T cells or other immune cells. In this review, we summarize current phase I/II clinical trials evaluating novel immunotherapies targeting stimulatory pathways and outline their advantages, limitations, and future directions.
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- 2021
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13. Emerging therapeutic agents for advanced non-small cell lung cancer
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Ruqin Chen, Rami Manochakian, Lauren James, Abdel-Ghani Azzouqa, Huashan Shi, Yan Zhang, Yujie Zhao, Kexun Zhou, and Yanyan Lou
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Advanced non-small cell lung cancer ,NSCLC ,Emerging therapeutic agents ,Targeted therapy ,Immunotherapy ,Clinical trials ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
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- 2020
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14. Survival of Black and White Patients With Stage IV Small Cell Lung Cancer
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Huashan Shi, Kexun Zhou, Jordan Cochuyt, David Hodge, Hong Qin, Rami Manochakian, Yujie Zhao, Sikander Ailawadhi, Alex A. Adjei, and Yanyan Lou
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stage IV Small cell lung cancer ,racial ,socioeconomic status ,survival ,academic program ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundSmall cell lung cancer (SCLC) is associated with aggressive biology and limited treatment options, making this disease a historical challenge. The influence of race and socioeconomic status on the survival of stage IV SCLC remains mostly unknown. Our study is designed to investigate the clinical survival outcomes in Black and White patients with stage IV SCLC and study the demographic, socioeconomic, clinical features, and treatment patterns of the disease and their impact on survival in Blacks and Whites.Methods and ResultsStage IV SCLC cases from the National Cancer Database (NCDB) diagnosed between 2004 and 2014 were obtained. The follow-up endpoint is defined as death or the date of the last contact. Patients were divided into two groups by white and black. Features including demographic, socioeconomic, clinical, treatments and survival outcomes in Blacks and Whites were collected. Mortality hazard ratios of Blacks and Whites stage IV SCLC patients were analyzed. Survival of stage IV SCLC Black and White patients was also analyzed. Adjusted hazard ratios were analyzed by Cox proportional hazards regression models. Patients’ median follow-up time was 8.18 (2.37-15.84) months. Overall survival at 6, 12, 18 and 24 months were 52.4%, 25.7%, 13.2% and 7.9% in Blacks in compared to 51.0%, 23.6%, 11.5% and 6.9% in Whites. White patients had significantly higher socioeconomic status than Black patients. By contrast, Blacks were found associated with younger age at diagnosis, a significantly higher chance of receiving radiation therapy and treatments at an academic/research program. Compared to Whites, Blacks had a 9% decreased risk of death.ConclusionOur study demonstrated that Blacks have significant socioeconomic disadvantages compared to Whites. However, despite these unfavorable factors, survival for Blacks was significantly improved compared to Whites after covariable adjustment. This may be due to Blacks with Stage IV SCLC having a higher chance of receiving radiation therapy and treatments at an academic/research program. Identifying and removing the barriers to obtaining treatments at academic/research programs or improving the management in non-academic centers could improve the overall survival of stage IV SCLC.
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- 2021
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15. Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR
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Karan Seegobin, Umair Majeed, Nathaniel Wiest, Rami Manochakian, Yanyan Lou, and Yujie Zhao
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targeted mutations ,immunotherapy ,c-MET ,RET ,BRAF ,ROS-1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
While first line targeted therapies are the current standard of care treatment for non-small cell lung cancer (NSCLC) with actionable mutations, the cancer cells inevitably acquire resistance to these agents over time. Immune check-point inhibitors (ICIs) have improved the outcomes of metastatic NSCLC, however, its efficacy in those with targetable drivers is largely unknown. In this manuscript, we reviewed the published data on ICI therapies in NSCLC with ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 (ERBB2) alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the BRAF (0–54%), c-MET (12–49%), and KRAS (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in RET fusion NSCLC (less than10% in all studies but one) and ALK fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of ROS1 fusion, NTRK fusion, and HER 2 mutant NSCLC were 0–17%, 50% and 7–23%, respectively, making the efficacy of ICIs in these groups of patients less clear. In most studies, no significant correlation between treatment outcome and PD-L1 expression or tumor mutation burden (TMB) was identified, and how to select patients with NSCLC harboring actionable mutations who will likely benefit from ICI treatment remains unknown.
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- 2021
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16. Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
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Nathaniel Wiest, Umair Majeed, Karan Seegobin, Yujie Zhao, Yanyan Lou, and Rami Manochakian
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Non-small cell lung cancer ,lung cancer ,EGFR ,tyrosine kinase inhibitor ,immune-mediated adverse effects ,immune checkpoint inhibitor (ICI) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.
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- 2021
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17. Crizotinib‐associated renal cyst development may be associated with prolonged progression‐free survival in patients with ALK‐positive non‐small‐cell lung cancer: Case report and review of the literature
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Nathaniel E. Wiest, Katherine S. Tzou, Matthew T. Olson, Steven M. Herchko, Essa M. Bajalia, David D. Thiel, Yanyan Lou, Yujie Zhao, and Rami Manochakian
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ALK positive ,crizotinib ,non‐small‐cell lung cancer ,progression‐free survival ,renal cysts ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract Non‐small cell lung cancer patients with anaplastic lymphoma kinase or c‐ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib‐associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression‐free survival.
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- 2021
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18. A Panel Evaluation of the Changes in the General Public’s Social-Media-Following of United States’ Public Health Departments during COVID-19 Pandemic
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Areej Khokhar, Aaron Spaulding, Zuhair Niazi, Sikander Ailawadhi, Rami Manochakian, Asher Chanan-khan, Shehzad Niazi, and Taimur Sher
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.
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- 2021
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19. Patients with high-grade alectinib-induced skin rash: How do we desensitize these patients? A case report and review of literature
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Karan Seegobin, Umair Majeed, Yanyan Lou, Yujie Zhao, and Rami Manochakian
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Medicine (General) ,R5-920 - Abstract
With the advent of targeted therapy for non-small-cell lung cancer, there are many new available treatment options for patients whose cancer harbors an actionable mutation or alteration. These new medications come with numerous side effects, for some of which, the management is not well defined. Alectinib is a second-generation tyrosine kinase inhibitor approved for stage-IV lung adenocarcinoma with anaplastic lymphoma kinase gene rearrangement. Severe (⩾Grade 3) skin rash is a rare side effect of alectinib. Reintroducing alectinib in patients with severe skin rash is not well defined in the medical literature. While other case reports have outlined their approach and desensitization protocol, the maximum dose that patients were titrated up to in a desensitization protocol was 300 mg twice daily. Here, we report a case of Grade 3 skin rash secondary to alectinib, and our experience in managing the rash and reintroducing alectinib with a unique desensitization protocol to a max of 600 mg twice daily (full dose). This case could provide further guidance to oncologists managing patients with this adverse event and may aid in reducing concerns to both patients and physicians about recurrence of skin rash at the maximum dose.
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- 2020
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20. Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
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Aixa E. Soyano, Bhagirathbhai Dholaria, Julian A. Marin-Acevedo, Nancy Diehl, David Hodge, Yan Luo, Rami Manochakian, Saranya Chumsri, Alex Adjei, Keith L. Knutson, and Yanyan Lou
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Non-small cell lung cancer ,Nivolumab ,Pembrolizumab ,Anti-PD-1 ,Immunotherapy ,Relapse/progression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. Patient and methods We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. Results We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24–3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17–2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54–4.05; P
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- 2018
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21. Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases
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Moses O. Oyewumi, Adnan Alazizi, Daniel Wehrung, Rami Manochakian, and Fayez F. Safadi
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Cytology ,QH573-671 - Abstract
Lung cancer is the second most common cancer and the leading cause of cancer related mortality in both men and women. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. It is widely accepted that tumor metastasis is a formidable barrier to effective treatment of lung cancer. The bone is one of the frequent metastatic sites for lung cancer occurring in a large number of patients. Bone metastases can cause a wide range of symptoms that could impair quality of life of lung cancer patients and shorten their survival. We strongly believe that molecular targets (tumor-related and bone microenvironment based) that have been implicated in lung cancer bone metastases hold great promise in lung cancer therapeutics. Thus, this paper discusses some of the emerging molecular targets that have provided insights into the cascade of metastases in lung cancer with the focus on bone invasion. It is anticipated that the information gathered might be useful in future efforts of optimizing lung cancer treatment strategies.
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- 2014
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22. Impact of Benzodiazepine Use on Length of Stay and 30-Day ED Visits among Hospitalized Hematopoietic Stem Cell Transplant Recipients
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Shehzad K, Niazi, Madiha, Iqbal, Aaron C, Spaulding, Chanel, Wood, Rami, Manochakian, Aneel, Paulus, Sikander, Ailawadhi, Emily, Brennan, Mohamed A, Kharfan Dabaja, and Taimur, Sher
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Adult ,Hospitalization ,Benzodiazepines ,Hematopoietic Stem Cell Transplantation ,Humans ,General Medicine ,Length of Stay ,Emergency Service, Hospital - Abstract
This study assesses the impact of benzodiazepine (BNZ) use on length of stay (LOS) and 30-day emergency department (ED) visits after hematopoietic stem cell transplant (HSCT).Adult patients (18 years and older) who underwent an allogeneic or an autologous HSCT from 2015 to 2018 at the study site were included. Five multivariable models were used for both allogeneic and autologous HSCT: BNZ-naïve status, diazepam equivalent daily dosage (DEDD; 0 vs any), DEDD (excluding 0), ED visits, and LOS.BNZ-naïve autologous HSCT recipients were less likely to use any BNZs in the hospital (odds ratio [OR] 0.07,BNZ use resulted in increased 30-day ED visits after autologous HSCT. BNZ-naïve recipients were less likely to use BNZs during hospital stays; if they required BNZs, then it was in lower dosages.
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- 2022
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23. Social Media and Professional Development for Oncology Professionals
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Anusha Chidharla, Audun Utengen, Deanna J. Attai, Emily K. Drake, G.J. van Londen, Ishwaria M. Subbiah, Elizabeth Henry, Martina Murphy, Maura M. Barry, Rami Manochakian, Scott Moerdler, Stacy Loeb, Stephanie L. Graff, Yan Leyfman, Michael A. Thompson, and Merry J. Markham
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Oncology ,Oncology (nursing) ,Health Policy ,education ,Humans ,Medical Oncology ,Delivery of Health Care ,Social Media ,humanities ,health care economics and organizations - Abstract
The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.
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- 2023
24. Lung cancer in patients with Lynch Syndrome: Association or Coincidence?
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Umair Majeed, Karan Seegobin, Jason Lewis, Shenduo Li, Yujie Zhao, Yanyan Lou, and Rami Manochakian
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
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25. Chemoimmunotherapy as The First-Line Treatment for Patients with Extensive-Stage Small-Cell Lung Cancer and an ECOG Performance Status of 2 or 3
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Muskan Agarwal, Alex Liu, Blake T. Langlais, Konstantinos Leventakos, Nathan Y. Yu, Daniel Almquist, Rami Manochakian, and Vinicius Ernani
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
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26. From Boring to Bravo! Using Learning Science to Create Memorable Presentations
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Jennifer E. Schwartz, Sam Brondfield, Katherine Walsh, and Rami Manochakian
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General Medicine - Abstract
The practice of oncology continues to evolve over time. Educators find themselves in a position where they are no longer able to teach a topic in its entirety. Moreover, the rapid expansion of information available through research and discovery in the field of oncology makes it difficult for learners to process the constant barrage of new content. Lecturers continue to impart knowledge using didactic techniques, often trying to include as much material as possible in the time permitted. The question becomes: In the face of an impossibly large field, how can one assist learners in learning, and retaining, what is most important? The science of learning continues to develop, and we now recognize that there are ways to teach that optimally facilitate the retention and application of knowledge. By using these strategies, educators can make it easier for learners to absorb and retain key information. This article will touch upon several such techniques: cognitive load optimization, analogy, contrasting cases, elaboration, and just-in-time telling. By applying these methods to didactic presentations, educators can ensure that their lessons are heard, understood, and ultimately transformed into something unforgettable.
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- 2023
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27. Carbon ion radiotherapy in the management of non‐small cell lung cancer
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Danushka Seneviratne, Hitoshi Ishikawa, Jingfang Mao, Jingjing M. Dougherty, Aaron Bush, Mathew Thomas, Rami Manochakian, Yanyan Lou, Dawn Owen, Terence T. Sio, Jessica Kirwan, Stephen J. Ko, and Bradford S. Hoppe
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Oncology - Published
- 2022
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28. Trends in race and sex reporting in lung cancer phase III clinical trials
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Faaiq Aslam, Rami Manochakian, Yanyan Lou, Gerardo Colon-Otero, and Taimur Sher
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Background: To understand the changing trends in reporting of race and sex as a demographic variable in phase III lung cancer clinical trials published over the last 35 years. Methods: A total of 426 articles reporting results of phase 3 lung cancer clinical trials published from 1984 to 2019 were identified in PubMed. Statistical analysis on trends over time on percentage of minority and female participation were performed. Results: Only 137 (32.2%) of the 426 studies analyzed reported race of participants. Among those studies, we found that the mean participation rate of white participants was significantly higher (82.65%) (p < 0.001). We found a decrease in African American participants and an increase in Asian participants over time. When looking at sex, we found that although the rate of male participation (69.02%) was significantly higher than that of female participation (30.98%), the female participation has improved with time at a rate of 0.65% per year. Conclusions: We found that the reporting and participation of minority races continues to lag that of other demographic factors like sex in phase III clinical trials in lung cancer. Especially in African Americans, where the participation in lung cancer phase III clinical trials has declined despite the rising incidence in lung cancer.
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- 2023
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29. Using social media for patient-driven cancer research
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Rami, Manochakian and Don S, Dizon
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- 2022
30. Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer
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Shenduo Li, Guilherme Sacchi de Camargo Correia, Jing Wang, Rami Manochakian, Yujie Zhao, and Yanyan Lou
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Cancer Research ,Oncology - Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.
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- 2023
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31. Understanding Patient Perspective, Challenges, Behavioral Patterns, and Preferences Towards Participation in Multiple Myeloma Clinical Trials: A Prospective Study
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Sikander Ailawadhi, Jay R. Hydren, Leyla Bojanini, Nathan W. Sweeney, Felicia Seng, Mizba Baksh, Ahsan Rasheed, Mays Abdulazeez, Meghna Ailawadhi, Keren George, Ricardo D Parrondo, Vivek Roy, Victoria R. Alegria, Pooja Advani, Rami Manochakian, Jason S. Starr, Taimur Sher, Jennifer M. Ahlstrom, and Asher Chanan-Khan
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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32. Impact of Depression and Anxiety on Opioid Use in Hospitalized Hematopoietic Cell Transplantation Recipients
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Mohamed A. Kharfan-Dabaja, Aneel Paulus, Chanel Wood, Prachi Jani, Rami Manochakian, Madiha Iqbal, Steven C. Ames, Aaron Spaulding, Shehzad K. Niazi, Salman Ahmed, Asher Chanan-Khan, Vivek Roy, Taimur Sher, Sikander Ailawadhi, and Ernesto Ayala
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Adult ,Male ,medicine.medical_specialty ,Anxiety ,Drug overdose ,Odds ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Internal medicine ,mental disorders ,Humans ,Medicine ,Applied Psychology ,Depression (differential diagnoses) ,Aged ,Retrospective Studies ,Depression ,business.industry ,Incidence ,Hematopoietic Stem Cell Transplantation ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,030227 psychiatry ,Analgesics, Opioid ,Hospitalization ,Transplantation ,Psychiatry and Mental health ,Opioid ,Florida ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Hematopoietic cell recipients are reported to have a high prevalence of depression and anxiety. The impact of depression and anxiety on opioid use has not been well characterized. This is of significance as the opioid epidemic continues, and over 60% of deaths secondary to drug overdose involve the use of opioids.In this retrospective, single-center study of 275 patients who underwent hematopoietic cell transplantation (HCT) (allogeneic and autologous) for hematological malignancies, we explore the impact of depression and anxiety on opioid use.Patients who were both anxious and depressed at admission for HCT had increased odds of receiving an opioid (odds ratio of 4.50 [95% confidence interval: 1.75, 11.56]) compared with patients who were neither depressed nor anxious. However, patients who were either depressed or anxious did not have different odds of receiving an opioid compared with those who were neither depressed nor anxious. Autologous HCT recipients had reduced odds of receiving an opioid (odds ratio of 0.17 [95% confidence interval: 0.08, 0.38]) compared with patients undergoing allogeneic HCT. Patients with lower Karnofsky performance status (90 on a scale of 1-100) had an increased incidence of receiving a higher Morphine milligram equivalent daily dosage (incidence rate ratio of 2.59 [95% confidence interval: 1.18, 5.67]) when modeled by zero truncated negative binomial regression.Presence of depression and anxiety impacts opioid use in patients undergoing HCT.
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- 2020
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33. Quantitative Analysis of Oncology Professional Learning Preferences
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Allyson Baer, Rami Manochakian, Anne Grupe, Yu Shyr, Thomas J. George, Marie E. Wood, Jennifer Williams, Leora Horn, Maura Polansky, and Cathy Wang
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Oncology ,medicine.medical_specialty ,Oncology (nursing) ,Health Personnel ,Health Policy ,education ,MEDLINE ,Pilot Projects ,Medical Oncology ,Quantitative analysis (finance) ,Education, Professional ,Internal medicine ,Professional learning community ,Cohort ,medicine ,Humans ,Professional association ,Psychology - Abstract
PURPOSE: ASCO is the premier and largest global professional society for oncology care professionals. In 2015, ASCO launched a longitudinal Learning Cohort Pilot Project to catalog and better understand the learning behaviors and preferences of oncology health care providers. A secondary goal was to assess learner preferences and utilization related to ASCO’s portfolio of educational resources. METHODS: The Learning Cohort Pilot Project was conducted between November 2015 and August 2016 with 49 ASCO members. Participants were selected via convenience sampling and stratified random sampling to generate a cohort that mirrored the demographic distribution of overall ASCO membership. Participants completed a different ASCO resource-specific feedback activity each month, which measured professional educational needs, sources sought, and preferences for educational resources. Responses were organized by demographic variables in our participant pool to identify trends in provider learning preferences. Fisher’s exact test was used to assess the association between participant demographics and practice setting and responses. Holm’s procedure was used to adjust for multiple testing. RESULTS: The Learning Cohort Pilot Project revealed statistically significant relationships between participant demographic variables and learning preferences. Age and practice setting were the demographic variables most consistently associated with the different preferences explored throughout the targeted activities. CONCLUSION: The results of this pilot cohort reinforced the hypothesis that oncology care providers have different professional educational needs and preferences that can be potentially anticipated and met with tailored resources. Delivering solutions to meet these needs represents an opportunity for further research and resource development.
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- 2020
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34. Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab
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Robert W. Gao, Courtney N. Day, Nathan Y. Yu, Aaron Bush, Adam C. Amundson, Pranitha Prodduturvar, Umair Majeed, Emily Butts, Thomas Oliver, Anna J. Schwecke, Jenesse N. Moffett, David M. Routman, William G. Breen, Ashley L. Potter, Joel Rivera-Concepcion, Bradford S. Hoppe, Steven E. Schild, Terence T. Sio, Yanyan Lou, Vinicius Ernani, Stephen Ko, Kenneth R. Olivier, Kenneth W. Merrell, Yolanda I. Garces, Rami Manochakian, William S. Harmsen, Konstantinos Leventakos, and Dawn Owen
- Subjects
Pulmonary and Respiratory Medicine ,Radiation Pneumonitis ,Cancer Research ,Lung Neoplasms ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Antibodies, Monoclonal ,Humans ,Radiotherapy Dosage ,Chemoradiotherapy ,Pneumonia - Abstract
The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen.We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis.One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively.We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.
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- 2022
35. AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma
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Sikander Ailawadhi, Ricardo D. Parrondo, Navnita Dutta, Bing Han, Gina Ciccio, Yesesri Cherukuri, Victoria R. Alegria, Betsy R. LaPlant, Vivek Roy, Taimur Sher, Brett Edwards, Stephanie Lanier, Alak Manna, Keisha Heslop, Thomas Caulfield, Emir Maldosevic, Peter Storz, Rami Manochakian, Yan Asmann, Asher A. Chanan-Khan, and Aneel Paulus
- Subjects
Cancer Research ,Oncology ,multiple myeloma ,Bcl-2 inhibition ,apoptosis - Abstract
Bcl-2 and Mcl-1 proteins play a role in multiple myeloma (MM) cell survival, for which targeted inhibitors are being developed. AT-101 is an oral drug, which disrupts Bcl-2 and Mcl-1 function, impedes mitochondrial bioenergetic processes and induces apoptosis in MM cells. When combined with lenalidomide and dexamethasone (Rd), AT-101 significantly reduced tumor burden in an in vivo xenograft model of MM. These data provided rationale for a phase I/II study to establish the effective dose of AT-101 in combination with Rd (ARd regimen) in relapsed/refractory MM. A total of 10 patients were enrolled, most with high-risk cytogenetics (80%) and prior stem cell transplant (70%). Three patients were lenalidomide-refractory, 2 were bortezomib-refractory and 3 were daratumumab-refractory. The ARd combination was well tolerated with most common grade 3/4 adverse events being cytopenia’s. The overall response rate was 40% and clinical benefit rate was 90%. The median progression free survival was 14.9 months (95% CI 7.1-NE). Patients responsive to ARd showed a decrease in Bcl-2:Bim or Mcl-1:Noxa protein complexes, increased CD8+ T and NK cells and depletion of T and B-regulatory cells. The ARd regimen demonstrated an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM prompting further investigation in additional patients.
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- 2023
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36. Education and Training
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Hemant S. Murthy, Rami Manochakian, and Mohamed A. Kharfan-Dabaja
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education - Abstract
At the heart of every comprehensive cancer center is education and training. The prominence of a cancer center is often correlated to the strength of their educational and training programs. Education is responsible for training the next generation of clinicians, advanced practice providers, nurses, other supporting staff, and researchers. This chapter provides the framework of education and training, specific to different disciplines, within a comprehensive cancer center. In addition, it discusses education beyond training, such as maintaining educational standards, and developing new programs that embrace the continuous advances in cancer care.
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- 2021
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37. Survival Trends in Young Patients With Multiple Myeloma: A Focus on Racial-Ethnic Minorities
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Mays F Abdulazeez, Abdel Ghani Azzouqa, Meghna Ailawadhi, Vivek Roy, Prakash Vishnu, Victoria R. Alegria, Asher Chanan-Khan, David O. Hodge, Rami Manochakian, Aneel Paulus, Jordan J. Cochuyt, Prachi Jani, Sikander Ailawadhi, Taimur Sher, Salman Ahmed, and Ashna Grover
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Population ,Ethnic group ,Kaplan-Meier Estimate ,White People ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Epidemiology ,medicine ,Humans ,Healthcare Disparities ,education ,Survival analysis ,Aged ,education.field_of_study ,Relative survival ,business.industry ,Mortality rate ,Age Factors ,Ecological study ,Hispanic or Latino ,Hematology ,Middle Aged ,United States ,Black or African American ,Oncology ,Population Surveillance ,030220 oncology & carcinogenesis ,Cohort ,Female ,Multiple Myeloma ,business ,SEER Program ,030215 immunology ,Demography - Abstract
Outcomes in multiple myeloma (MM) have improved significantly over time. This is true overall for all patients as well as patient subgroups based on age and race/ethnicity. Despite this, disparities are noted in outcomes when looking at racial subgroups.We performed an analysis from the population-based Surveillance, Epidemiology, and End Results (SEER) database to evaluate improvement in relative survival rates (RSRs) for young (≤ 40 years at the time of MM diagnosis) and older (40 years at the time of MM diagnosis) over time by race/ethnicity, specifically focusing on Hispanic patients with MM. Expected survival was estimated using the age- and gender-specific death rates from the United States population. RSR was provided as the ratio of the observed to expected survival at individual time points. Five-year and 10-year RSRs were calculated for patients based on treatments modalities available in various time periods.We identified a total of 89,451 patients with MM in SEER, of which 1460 patients formed the young patients with MM (≤ 40 years) cohort. Five- and 10-year RSR improved significantly over time for all patients and older patients (40 years) by race (all P .001). Evaluating the younger patients, RSR improved significantly for non-Hispanic whites and non-Hispanic blacks, but not for Hispanics. This was true for the 5-year (P = .08) and 10-year (P = .13) RSRs.We report a lack of significant benefit in long-term outcomes for younger Hispanic patients with MM over time. This could be owing to multifactorial causes that need to be addressed to mitigate outcome disparities.
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- 2019
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38. Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia
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Aditya Mehta, Prakash Vishnu, Asher Chanan-Khan, Rami Manochakian, Suman Biswas, Aneel Paulus, Taimur Sher, Leyla Bojanini, Julian A. Marin-Acevedo, Sonikpreet Aulakh, Sikander Ailawadhi, Victoria R. Alegria, Meghna Ailawadhi, Vivek Roy, Madiha Iqbal, Winston Tan, and Vivek Kumar
- Subjects
Adult ,Male ,Risk ,medicine.medical_specialty ,Chronic lymphocytic leukaemia ,Multivariate analysis ,Adolescent ,Chronic lymphocytic leukemia ,Population ,lcsh:RC254-282 ,Article ,Young Adult ,Cancer Survivors ,Survivorship curve ,Internal medicine ,Epidemiology ,medicine ,Humans ,Young adult ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Leukemia, Lymphocytic, Chronic, B-Cell ,United States ,Leukemia ,Standardized mortality ratio ,Oncology ,Risk factors ,Multivariate Analysis ,Female ,business ,SEER Program - Abstract
With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p
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- 2019
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39. Outcomes of COVID-19 in Patients With Cancer: A Closer Look at Pre-Emptive Routine Screening Strategies
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Carrie A. Thompson, Andrew D. Badley, Christopher E. Wee, Thomas E. Witzig, Anuhya Kommalapati, Antoine N. Saliba, Julia E Wiedmeier-Nutor, Jithma P. Abeykoon, Nadine Abdallah, Zhuoer Xie, Sri Harsha Tella, Joshua C. Pritchett, Robert R. McWilliams, Daniel R. Almquist, Sagar Rakshit, Xavier Andrade-Gonzalez, Ashley Hickman, Naseema Gangat, Dipesh Uprety, Umair Majeed, Mariza de Andrade, Konstantinos Leventakos, Karl Sorenson, Rami Manochakian, Thorvardur R. Halfdanarson, Joleen M. Hubbard, Evandro D. Bezerra, Alan H. Bryce, and Sikander Ailawadhi
- Subjects
2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,QUALITY IN ACTION ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Intensive care medicine ,Early Detection of Cancer ,Routine screening ,Oncology (nursing) ,business.industry ,SARS-CoV-2 ,Health Policy ,Cancer ,COVID-19 ,Middle Aged ,medicine.disease ,Hospitalization ,Intensive Care Units ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
PURPOSE: The benefit of routine pre-emptive screening for severe acute respiratory syndrome coronavirus 2 infections in patients with cancer before cancer-directed therapies is unclear. Herein, we characterize the outcomes of a cohort of patients with cancer who were diagnosed with COVID-19 by routine screening (RS) in comparison with those diagnosed on the basis of clinical suspicion or exposure history (nonroutine screening [NRS]). METHODS: A multisite prospective observational study was conducted at three major and five satellite campuses of the Mayo Clinic Cancer Center between March 18 and July 31, 2020. The primary outcome was COVID-19–related hospital admission. Secondary outcomes included intensive care unit admissions and all-cause mortality. RESULTS: Five thousand four hundred fifty-two patients underwent RS in the outpatient setting only, and 44 (0.81%) were diagnosed with COVID-19. RS detected 19 additional patients from the scheduled inpatient admissions for surgical or interventional procedures or inpatient chemotherapy. One hundred sixty-one patients were diagnosed with COVID-19 on the basis of NRS. COVID-19–related hospitalization rate (17.5% v 26.7%; P = .14), intensive care unit admission (1.6% v 5.6%; P = .19), and mortality (4.8% v 3.7%; P = .72) were not significantly different between the RS and NRS groups. In the multivariable analysis, age ≥ 60 years (odds ratio, 4.4; P = .023) and an absolute lymphocyte count ≤ 1.4 × 109/L (odds ratio, 9.2; P = .002) were independent predictors of COVID-19–related hospital admission. CONCLUSION: The COVID-19 positivity rate was low on the basis of RS. Comparing the hospital admission and mortality outcomes with the NRS cohort, there were no significant differences. The value of routine pre-emptive screening of asymptomatic patients with cancer for COVID-19 remains low.
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- 2021
40. Crizotinib‐associated renal cyst development may be associated with prolonged progression‐free survival in patients with ALK‐positive non‐small‐cell lung cancer: Case report and review of the literature
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Steven Herchko, David D. Thiel, Rami Manochakian, Nathaniel E. Wiest, Essa M. Bajalia, Yujie Zhao, Katherine S. Tzou, Matthew T. Olson, and Yanyan Lou
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Medicine (General) ,medicine.drug_class ,Case Report ,Case Reports ,030204 cardiovascular system & hematology ,Tyrosine-kinase inhibitor ,renal cysts ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,ALK positive ,medicine ,Anaplastic lymphoma kinase ,Cyst ,Progression-free survival ,Lung cancer ,non‐small‐cell lung cancer ,crizotinib ,Oncogene ,Crizotinib ,business.industry ,progression‐free survival ,General Medicine ,medicine.disease ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Non small cell ,business ,medicine.drug - Abstract
Non‐small cell lung cancer patients with anaplastic lymphoma kinase or c‐ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib‐associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression‐free survival.
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- 2021
41. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends
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Yujie Zhao, Rami Manochakian, Yanyan Lou, and Umair Majeed
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Antineoplastic Agents ,Review ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Clinical Trials, Phase II as Topic ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Advanced disease ,Medicine ,Animals ,Humans ,In patient ,Diseases of the blood and blood-forming organs ,Molecular Targeted Therapy ,Precision Medicine ,Lung cancer ,Molecular Biology ,Protein Kinase Inhibitors ,RC254-282 ,Clinical Trials, Phase I as Topic ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Hematology ,medicine.disease ,Phase I/II clinical trials ,respiratory tract diseases ,Clinical trial ,ErbB Receptors ,030104 developmental biology ,Advanced NSCLC ,030220 oncology & carcinogenesis ,First-in-human ,Non small cell ,Personalized medicine ,RC633-647.5 ,business ,Early phase - Abstract
Lung cancer remains the leading cause of cancer-related mortality in both men and women in the US and worldwide. Non-small cell lung cancer is the most common variety accounting for 84% of the cases. For a subset of patients with actionable mutations, targeted therapy continues to provide durable responses. Advances in molecular and immunohistochemical techniques have made it possible to usher lung cancer into the era of personalized medicine, with the patient getting individualized treatment based on these markers. This review summarizes the recent advances in advanced NSCLC targeted therapy, focusing on first-in-human and early phase I/II clinical trials in patients with advanced disease. We have divided our discussion into different topics based on these agents' mechanisms of action. This article is aimed to be the most current review of available and upcoming targeted NSCLC treatment options. We will also summarize the currently available phase I/II clinical trial for NSCLC patients at the end of each section.
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- 2021
42. A Panel Evaluation of the Changes in the General Public’s Social-Media-Following of United States’ Public Health Departments during COVID-19 Pandemic
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Rami Manochakian, Sikander Ailawadhi, Areej Khokhar, Asher Chanan-Khan, Shehzad K. Niazi, Zuhair Niazi, Taimur Sher, and Aaron Spaulding
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risk-communication ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,health promotion ,social media ,Information Seeking Behavior ,New York ,lcsh:Computer applications to medicine. Medical informatics ,California ,03 medical and health sciences ,Government Agencies ,0302 clinical medicine ,Information seeking behavior ,Pandemic ,Humans ,Medicine ,Risk communication ,Social media ,030212 general & internal medicine ,Pandemics ,Original Research ,Community and Home Care ,SARS-CoV-2 ,business.industry ,Communication ,030503 health policy & services ,Public health ,lcsh:Public aspects of medicine ,public health ,Public Health, Environmental and Occupational Health ,COVID-19 ,lcsh:RA1-1270 ,Public relations ,United States ,humanities ,Health promotion ,Internet Use ,Florida ,lcsh:R858-859.7 ,Emergencies ,0305 other medical science ,business - Abstract
Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.
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- 2021
43. Mutational profile, clinical characterization, and outcomes of lung cancer in solid organ transplant recipients
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Shenduo Li, Rami Manochakian, Yujie Zhao, and Yanyan Lou
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Cancer Research ,Oncology - Abstract
e21131 Background: Solid organ transplant recipients have increased risk for malignancies. Lung cancer is the second most common malignancy in this population. Those patients are usually on long-term immunosuppressive medications that may affect tumorigenesis, cancer characteristics, and treatment response. Previous studies have investigated the characteristics and outcomes of post-transplant patients with lung cancer in small-sized cohorts. However, the tumor mutational profile and detailed treatment response at different stages have not been reported. Methods: We conducted a retrospective study from a cohort of 52 solid organ transplant recipients who were diagnosed with lung cancer at Mayo Clinic from 2018 to 2021. We examined tumor molecular alteration using next generation sequencing (NGS), analyzed the treatment modalities, progression-free survival (PFS), and overall survival (OS) and compared those to the general population with lung cancer using historical data in previous large trials. Results: In our study, most transplanted solid organs are kidney (N = 28, 53.8%), followed by liver (N = 12, 23.1%) and heart (N = 9, 17.3%). The adenocarcinoma (N = 28, 53.8%) represented the most common histology, followed by squamous cell carcinoma (N = 19, 36.5%). It consisted of Stage I (30.8%), stage II (15.4%), stage III (25%), and stage IV (26.9%). The most common site of metastasis is bone (64.3%). Transplant recipients with lung cancer have a significantly high frequency of somatic BRCA 1/2 mutations (30.4%), compared to the general population with advanced lung cancer (2.1%, p < 0.001). The frequencies of TP53 mutations (52.2%) and EGFR mutations (30.4%) are also increased. For stage I patients who received surgery or radiation therapy, the disease-free survival (DFS) is 16.5 months. 9 of 14 stage IV patients received chemotherapy. The median number of cycles received is 4. The median PFS is 4.9 months, and the median OS of all stage IV patients is 6.1 months. 4 patients were found to have actionable EGFR mutations, and 3 of them were initially diagnosed with stage IIIA and received Osimertinib after progression. One stage IV patient who was post-liver transplant received pembrolizumab for up to 5 cycles before he developed aspiration pneumonia and then pursued hospice. The PFS is 3.7 months. No immune-related adverse event was reported. Conclusions: In our cohort of solid organ transplant recipients who developed lung cancer, we observed a much higher frequency of somatic BRCA 1/2 mutations, compared to the general population with lung cancer. In addition, our data suggested post-transplant patients with stage I lung cancer have a shorter disease-free survival, and patients with stage IV lung cancer have a shorter overall survival, compared to the general population with lung cancer. Further study containing a high number of solid transplant patients to validate these findings is warranted.
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- 2022
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44. P40.18 Second Line Immunotherapy After Progression on a Different First Line Immunotherapy in Advanced Non-Small Cell Lung Cancer With Focus On Elderly
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Umair Majeed, Rami Manochakian, Y. Lou, Yujie Zhao, H. Shi, Karan Seegobin, and K. Zhou
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Focus (computing) ,business.industry ,medicine.medical_treatment ,First line ,Immunotherapy ,medicine.disease ,Second line ,Internal medicine ,medicine ,Non small cell ,Lung cancer ,business - Published
- 2021
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45. Association of Race, Socioeconomic Factors, and Treatment Characteristics With Overall Survival in Patients With Limited-Stage Small Cell Lung Cancer
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Yujie Zhao, Rami Manochakian, David O. Hodge, Huashan Shi, Kexun Zhou, Sikander Ailawadhi, Jordan J. Cochuyt, Yanyan Lou, and Ruqin Chen
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Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,MEDLINE ,Disease ,Race (biology) ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Socioeconomic status ,Original Investigation ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Proportional hazards model ,Research ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Treatment characteristics ,Small Cell Lung Carcinoma ,Survival Analysis ,United States ,Race Factors ,Online Only ,Oncology ,Social Class ,Female ,business - Abstract
Key Points Question Are disparities in race and socioeconomic status associated with outcomes among patients with limited-stage small cell lung cancer? Findings In this cohort study including 72 409 patients, data from the National Cancer Database indicated that members of racial minorities, including African American and Asian patients, have better survival than White patients. Other factors associated with better survival were female sex, high income, high education, private insurance, diagnostic confirmation by positive cytological analysis, increase in number of sampled regional lymph nodes, and earlier stage at diagnosis. Meaning These findings highlight the disparities in race and socioeconomic factors associated with outcomes of limited-stage small cell lung cancer., This cohort study investigates the associations of race, socioeconomic factors, and treatment characteristics with overall survival (OS) among patients with limited-stage small cell lung cancer (SCLC)., Importance It has been established that disparities in race and socioeconomic status are associated with outcomes of non–small cell lung cancer. However, it remains unknown whether this extends to stage I, II, or III small cell lung cancer (SCLC), or limited-stage SCLC (L-SCLC). Objective To investigate the associations of race, socioeconomic factors, and treatment characteristics with survival among patients with L-SCLC. Design, Setting, and Participants Demographic information for patients with L-SCLC diagnosed between 2004 and 2014 was obtained from the National Cancer Database. The follow-up end point is death or last follow-up (date of last contact). Patients were divided into 5 mutually exclusive cohorts by race. Data analysis was performed in October 2019. Main Outcomes and Measures Cox proportional hazards models were used to calculate univariable and multivariable models. Multivariable analyses were conducted to assess the associations of race and socioeconomic factors with risk-adjusted outcomes. Overall survival between groups was depicted by Kaplan-Meier curves. Results Of 72 409 patients analyzed (median [range] age, 67.0 [23.0-90.0] years), 40 289 (55.6%) were women. The distribution of disease stage was 10 619 patients (14.7%) with stage I disease, 7689 patients (10.6%) with stage II disease, and 54 101 patients (74.7%) with stage III disease. The median (range) duration of follow-up was 8.2 (2.4-15.8) months. Compared with White patients, the hazard of death decreased to 0.92 (95% CI, 0.89-0.95; P
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- 2021
46. Initial treatment of patients with thyroid cancer: Outcomes and factors associated with care at academic versus nonacademic cancer centers
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Rami Manochakian, Chander Shekher Aggarwal, Ana Maria Chindris, Mays F Abdulazeez, Shishir David, Sikander Ailawadhi, Hebah Alhumaidi, David O. Hodge, Robert C. Smallridge, Suman Biswas, and Jordan J. Cochuyt
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Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Cancer Care Facilities ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Follicular phase ,medicine ,Initial treatment ,Humans ,030212 general & internal medicine ,Thyroid Neoplasms ,Thyroid cancer ,Socioeconomic status ,Academic Medical Centers ,business.industry ,Hazard ratio ,Cancer ,medicine.disease ,United States ,Treatment Outcome ,Oncology ,Socioeconomic Factors ,030220 oncology & carcinogenesis ,Ethnic and Racial Minorities ,Female ,Hormone therapy ,business - Abstract
Background Factors associated with receiving initial care for thyroid cancer (TC) at academic centers (ACs) versus nonacademic centers (NACs) and their impact on patient outcomes have not been reported. Methods The National Cancer Database with TC cases from 2004 to 2013 was evaluated for association of type of center for initial care with socioeconomic factors and disease and treatment characteristics, as well as overall survival (OS; all-cause mortality). Results The patients with TC (n = 200,824) included were predominantly women (74%), non-Hispanic Whites (85%), and from metro areas (84%). Sixty percent received initial care at a NAC. There were no significant differences between treatment groups by age or gender. Among those treated at an AC, a higher proportion belonged to racial/ethnic minorities (16.5%) versus at a NAC (11.6%). Hormone therapy was used more in an AC versus a NAC (60% vs 47%). Patients with all TC pathologies combined had a lower likelihood of death when they received initial care at an AC (hazard ratio [HR], 0.948; P = .0006). Among individual pathologic subtypes, a lower likelihood of death was noted when initial care was received at an AC for follicular (HR, 0.828, P = .0010) and Hurthle cell cancers (HR, 792; P = .0008), as well as stage II papillary thyroid cancer (HR, 0.828; P = .0026), but not for other histopathologic subtypes. Conclusions Initial care at an AC was associated with lower likelihood of death for patients with TC, especially for those with follicular or Hurthle cell subtypes. Optimal resource use with consideration of patients' socioeconomic and demographic factors is imperative to ensure the most appropriate management of patients with TC in various treatment settings.
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- 2020
47. Patients with high-grade alectinib-induced skin rash: How do we desensitize these patients? A case report and review of literature
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Umair Majeed, Rami Manochakian, Karan Seegobin, Yanyan Lou, and Yujie Zhao
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Alectinib ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,desensitization ,Case Report ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Anaplastic lymphoma kinase ,Lung cancer ,030304 developmental biology ,Desensitization (medicine) ,0303 health sciences ,lcsh:R5-920 ,business.industry ,Treatment options ,General Medicine ,anaplastic lymphoma kinase ,medicine.disease ,Rash ,skin rash ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,lcsh:Medicine (General) - Abstract
With the advent of targeted therapy for non-small-cell lung cancer, there are many new available treatment options for patients whose cancer harbors an actionable mutation or alteration. These new medications come with numerous side effects, for some of which, the management is not well defined. Alectinib is a second-generation tyrosine kinase inhibitor approved for stage-IV lung adenocarcinoma with anaplastic lymphoma kinase gene rearrangement. Severe (⩾Grade 3) skin rash is a rare side effect of alectinib. Reintroducing alectinib in patients with severe skin rash is not well defined in the medical literature. While other case reports have outlined their approach and desensitization protocol, the maximum dose that patients were titrated up to in a desensitization protocol was 300 mg twice daily. Here, we report a case of Grade 3 skin rash secondary to alectinib, and our experience in managing the rash and reintroducing alectinib with a unique desensitization protocol to a max of 600 mg twice daily (full dose). This case could provide further guidance to oncologists managing patients with this adverse event and may aid in reducing concerns to both patients and physicians about recurrence of skin rash at the maximum dose.
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- 2020
48. Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8(+) T-cell responses
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Asher Chanan-Khan, Eduardo N. Chini, Fabio Malavasi, Keith L. Knutson, Javier Pinilla-Ibarz, Taimur Sher, Sonikpreet Aulakh, Nicole Lamanna, Aneel Paulus, Alak Manna, Sikander Ailawadhi, Laura J. Lewis-Tuffin, Rami Manochakian, Timothy Kellett, and Navnita Dutta
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B-Lymphocytes, Regulatory ,Immunobiology and Immunotherapy ,Chemistry ,Chronic lymphocytic leukemia ,FOXP3 ,chemical and pharmacologic phenomena ,hemic and immune systems ,Hematology ,CD38 ,CD8-Positive T-Lymphocytes ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,T-Lymphocytes, Regulatory ,Interleukin 10 ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Cancer research ,Tumor Microenvironment ,Cytotoxic T cell ,Humans ,IL-2 receptor ,CD5 ,CD8 ,Immunosuppressive Agents - Abstract
Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.
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- 2020
49. Timeliness of Initial Therapy in Multiple Myeloma: Trends and Factors Affecting Patient Care
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Victoria R. Alegria, Vivek A. Kumar, Rami Manochakian, Asher Chanan-Khan, Taimur Sher, Aneel Paulus, Salman Ahmed, Muhamad Alhaj-Moustafa, Leyla Bojanini, Zan Tahir Shareef, Ashna Grover, Prakash Vishnu, Srilekha Bodepudi, Meghna Ailawadhi, Vivek Roy, Sikander Ailawadhi, and Prachi Jani
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medicine.medical_specialty ,MEDLINE ,Patient care ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Health care ,medicine ,Humans ,Healthcare Disparities ,Multiple myeloma ,Aged, 80 and over ,Medically Uninsured ,Oncology (nursing) ,business.industry ,Medicaid ,Health Policy ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,United States ,Oncology ,030220 oncology & carcinogenesis ,Female ,Patient Care ,business ,Multiple Myeloma ,030215 immunology ,Patient education - Abstract
Multiple myeloma (MM) treatment has advanced significantly over the last 2 decades. In most patients, the disease course has been altered from early fatality to chronic morbidity with multiple lines of treatment. The MM treatment paradigm has shifted toward treating patients before end-organ damage occurs. Thus, timeliness of treatment initiation in this era might improve patient outcomes. This is the first report to our knowledge analyzing disparities and trends in treatment timeliness of patients with MM using the National Cancer Database. Multiple factors affected the timing of treatment initiation in MM and disparities were found. We noted that initiation of treatment was delayed in women (odds ratio [OR], 1.15; 95% CI, 1.1 to 1.2) and blacks (OR, 1.21; 95% CI, 1.14 to 1.28; reference, whites) and in patients diagnosed in more recent years (2012-2015; OR, 1.15; 95% CI, 1.1 to 1.22; reference, 2004-2007). Patients were likely to start treatment earlier if they were age ≥ 80 years (OR, 0.83; 95% CI, 0.76 to 0.9; reference, age < 60 years), were uninsured (OR, 0.81; 95% CI, 0.72 to 0.91; reference, private insurance), had Medicaid (OR, 0.87; 95% CI, 0.79 to 0.95; reference, private insurance), were treated in a comprehensive community cancer program (OR, 0.7; 95% CI, 0.65 to 0.77; reference, community cancer program), lived in a location other than the US Northeast, or had a higher Charlson comorbidity score. Patient education and income levels did not affect time to treatment initiation. Particular aspects of these disparities could be explained by our current health care system and insurance rules, whereas others need to be investigated more deeply.
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- 2020
50. Survival trends among non‐small‐cell lung cancer patients over a decade: impact of initial therapy at academic centers
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Rami Manochakian, Yanyan Lou, Jordan J. Cochuyt, Bhagirathbhai Dholaria, Robert C. Miller, Alex A. Adjei, David O. Hodge, Sikander Ailawadhi, Aixa E. Soyano, Neal M. Patel, Stephen J. Ko, Mathew Thomas, and Margaret M. Johnson
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Databases, Factual ,030204 cardiovascular system & hematology ,Time-to-Treatment ,03 medical and health sciences ,Community center ,0302 clinical medicine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Overall survival ,medicine ,Initial treatment ,Humans ,Radiology, Nuclear Medicine and imaging ,Initial therapy ,Lung cancer ,non‐small‐cell lung cancer ,outcome disparities ,Original Research ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Academic Medical Centers ,business.industry ,Incidence ,academic center ,Cancer ,Clinical Cancer Research ,treatment center type ,Middle Aged ,medicine.disease ,Survival Analysis ,community center ,National Cancer Database ,030220 oncology & carcinogenesis ,Female ,Non small cell ,business - Abstract
Background Treatment of non‐small‐cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. Methods The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. Results A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow‐up and OS for all patients were 11.8 months (range: 0‐133.6 months) and 13.1 months (95% CI: 13.08‐13.17), respectively. Median OS improved significantly for those diagnosed in 2010‐2013 (14.8 months [95% CI: 14.7‐14.9]) as compared to 2004‐2009 (12.4 months [95% CI: 12.3‐12.5]) (P
- Published
- 2018
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