Non-Small Cell Lung Cancer Discussion

find a primary research article on Use of immunotherapy in Non-small cell lung cancer treatment then write the summary. the summary should include Author and Title of article (published in 2016 or later), a PDF copy of the paper and a 5 -10 sentence summary of the findings.

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

Keywords: Non-small cell lung cancer, Immunotherapy, Programmed cell death protein 1
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INTRODUCTION
Immune checkpoint proteins, such as PD-1 or CTLA-4 emerged as promising targets of immunotherapy, and have improved clinical outcomes of non-small-cell lung cancer (NSCLC) patients tremendously. Currently, the anti-PD-1 agent pembrolizumab is approved for use as first- and second-line therapy in patients with advanced NSCLC whose tumors express PD-L1 in immunohistochemistry analysis (1,2). Nivolumab (anti-PD-1) and atezolizumab (anti-PD-L1) are both indicated for use as second-line therapies regardless of PD-L1 expression (1,3). Durvalumab (anti-PD-L1) is approved as a maintenance therapy in patients with unresectable, stage 3 NSCLC whose disease has not progressed following concurrent platinum-based chemoradiotherapy (4). However, many issues are still not resolved regarding the biomarker status, choice in the first-line setting, immunotherapy in oncogene-addicted tumors, and how to combine immunotherapy with other agents.

NSCLC is a heterogeneous disease that is categorized into 2 broad histologic subtypes, adenocarcinoma and squamous cell carcinoma. Recent investigation of tumor immune microenvironment suggested that lung adenocarcinoma and squamous cell carcinoma show significant differences in immune landscape (5). Understanding the differences in immune microenvironment may suggest heterogeneous response to immunotherapy. Several microenvironmental factors differentially induce lung adenocarcinoma and squamous cell carcinoma immune subtypes, as well as immune checkpoint expression (6). For example, tumor-associated macrophages are key immune cells in lung squamous cell carcinoma, whereas regulatory B cells play immunosuppressive role in lung adenocarcinoma. In addition, the complexity of immune landscape of NSCLC arises from molecular subtype, oncogenic drivers, nonsynonymous mutational load, tumor aneuploidy, clonal heterogeneity and tumor evolution (7).

Tumor expression of PD-L1 has been most widely investigated as a predictive marker of response, but the sensitivity and specificity of this approach is modest (8,9). PD-L1 testing shows variable results because of the different Abs and cutoff values used (10), thus PD-L1 alone cannot accurately reflect the complexity of the tumor microenvironment involved in the response to immunotherapy. At the genomic level, tumor mutational burden (TMB) has been correlated with the clinical response to anti-PD-1 therapy and associated with favorable responses in smokers (11). The role of TMB as a marker predictive of response has been also evaluated in several clinical trials (CheckMate026, CheckMate568, CheckMate227) (12,13,14), which showed that patients with high TMB showed enhanced response to immunotherapy, regardless of PD-L1 expression. However, overall survival (OS) was not affected by TMB alone, and further understanding of the role of TMB as a biomarker is warranted before the integration into clinical practice.

Important information for writing discussion questions and participation

Welcome to class

Hello class and welcome to the class and I will be your instructor for this course. This is a -week course and requires a lot of time commitment, organization, and a high level of dedication. Please use the class syllabus to guide you through all the assignments required for the course. I have also attached the classroom policies to this announcement to know your expectations for this course. Please review this document carefully and ask me any questions if you do. You could email me at any time or send me a message via the “message” icon in halo if you need to contact me. I check my email regularly, so you should get a response within 24 hours. If you have not heard from me within 24 hours and need to contact me urgently, please send a follow up text to

I strongly encourage that you do not wait until the very last minute to complete your assignments. Your assignments in weeks 4 and 5 require early planning as you would need to present a teaching plan and interview a community health provider. I advise you look at the requirements for these assignments at the beginning of the course and plan accordingly. I have posted the YouTube link that explains all the class assignments in detail. It is required that you watch this 32-minute video as the assignments from week 3 through 5 require that you follow the instructions to the letter to succeed. Failure to complete these assignments according to instructions might lead to a zero. After watching the video, please schedule a one-on-one with me to discuss your topic for your project by the second week of class. Use this link to schedule a 15-minute session. Please, call me at the time of your appointment on my number. Please note that I will NOT call you.

Please, be advised I do NOT accept any assignments by email. If you are having technical issues with uploading an assignment, contact the technical department and inform me of the issue. If you have any issues that would prevent you from getting your assignments to me by the deadline, please inform me to request a possible extension. Note that working fulltime or overtime is no excuse for late assignments. There is a 5%-point deduction for every day your assignment is late. This only applies to approved extensions. Late assignments will not be accepted.

If you think you would be needing accommodations due to any reasons, please contact the appropriate department to request accommodations.

Plagiarism is highly prohibited. Please ensure you are citing your sources correctly using APA 7th edition. All assignments including discussion posts should be formatted in APA with the appropriate spacing, font, margin, and indents. Any papers not well formatted would be returned back to you, hence, I advise you review APA formatting style. I have attached a sample paper in APA format and will also post sample discussion responses in subsequent announcements.

Your initial discussion post should be a minimum of 200 words and response posts should be a minimum of 150 words. Be advised that I grade based on quality and not necessarily the number of words you post. A minimum of TWO references should be used for your initial post. For your response post, you do not need references as personal experiences would count as response posts. If you however cite anything from the literature for your response post, it is required that you cite your reference. You should include a minimum of THREE references for papers in this course. Please note that references should be no more than 5 years old except recommended as a resource for the class. Furthermore, for each discussion board question, you need ONE initial substantive response and TWO substantive responses to either your classmates or your instructor for a total of THREE responses. There are TWO discussion questions each week, hence, you need a total minimum of SIX discussion posts for each week. I usually post a discussion question each week. You could also respond to these as it would count towards your required SIX discussion posts for the week.

I understand this is a lot of information to cover in 5 weeks, however, the Bible says in Philippians 4:13 that we can do all things through Christ that strengthens us. Even in times like this, we are encouraged by God’s word that we have that ability in us to succeed with His strength. I pray that each and every one of you receives strength for this course and life generally as we navigate through this pandemic that is shaking our world today. Relax and enjoy the course!

Hi Class,

Please read through the following information on writing a Discussion question response and participation posts.

Contact me if you have any questions.

Important information on Writing a Discussion Question

• Your response needs to be a minimum of 150 words (not including your list of references)
• There needs to be at least TWO references with ONE being a peer reviewed professional journal article.
• Include in-text citations in your response
• Do not include quotes—instead summarize and paraphrase the information
• Follow APA-7th edition
• Points will be deducted if the above is not followed

Participation –replies to your classmates or instructor

• A minimum of 6 responses per week, on at least 3 days of the week.
• Each response needs at least ONE reference with citations—best if it is a peer reviewed journal article
• Each response needs to be at least 75 words in length (does not include your list of references)
• Responses need to be substantive by bringing information to the discussion or further enhance the discussion. Responses of “I agree” or “great post” does not count for the word count.
• Follow APA 7th edition
• Points will be deducted if the above is not followed

• Remember to use and follow APA-7th edition for all weekly assignments, discussion questions, and participation points.
• Here are some helpful links
• The is a great resource