Original Work Product Progress Assessment

Introduction and Statement of Purpose

Through my original work and product, I hope to develop insight into the clinical research aspect
of oncology and gain real-world experience within the medical oncology field. With this, I hope
to write a fully developed medical analysis of the common side effects of PD-1 blocking
immunotherapies such as Nivolumab and Pembrolizumab that modern oncologists prescribe their
patients. I plan to gather data from the treatment experiences of eighty-three of Texas Oncology
Flower Mound’s patients who underwent either Opdivo (Nivolumab) or Keytruda
(Pembrolizumab) to create my analysis. I will look into specific parameters of patient response
including but not limited to tumor progression, side effects, side effect treatment, and continuity
of the drug. After thoroughly studying the patients’ response to the drugs and gathering my data,
I will move on to creating a spreadsheet to compile the data I collect into a compact form. The
final and most important aspect of my original work is completing the actual written component
and writing my findings from data collecting into the format of a professional medical paper.
Through this project, I will get well-rounded experience in the oncology field and be able to
share my knowledge in a scientific fashion.

Initial Research

Objective:
Going into a large research project on a topic I am only briefly familiar with was daunting and
required me to do a lot of research before jumping into the data collecting process. By
completing this initial step of reading research papers from other oncologists, basic
immunotherapy explanations, and articles on specific areas Dr. Bhogaraju highlighted, I hoped to
gain the groundwork of knowledge required to complete my original work. For example, in order
for me to successfully identify particular side effects of Opdivo and Keytruda, I would need to
know how to distinguish body reactions that result from immunotherapy from effects of other
sources. In addition, oncologists have to commonly keep up with new studies in the constantly
developing field so by completing this step, I am also practicing the active learning skills
required to be successful in oncology.

Materials:
● Campbell Biology: Immune System and Processes
● Principles of Cancer Immunotherapy (uptodate.com)
● Toxicities Associated With Checkpoint Inhibitor Immunotherapy (uptodate.com)
● FDA.org

Description of Process:
After discussing this project with me, my mentor provided me with two articles from a website
commonly used by medical professionals to keep up with breakthroughs in clinical research
called uptodate.com. However, as I started reading the article, I realized that I lacked knowledge
of the immune system to understand the articles completely. Due to this, I took the step to read
the immune system chapter in the Campbell Biology book before moving onto the articles. As
these articles were lengthy and greatly detailed, I paid particular attention to the interactions
between PD-1 and PD-L1, how such PD-1 blocking drugs work, how checkpoint inhibiting
drugs like Opdivo and Keytruda work, and side effects (irAEs) of common immunotherapy
drugs. Next, I went on the FDA releases for Nivolumab and Pembrolizumab to read about other
clinical studies that analyzed the effects of these specific drugs so I could see what to keep a
specific eye on. After gaining this rudimentary knowledge on checkpoint inhibiting drugs, I
could move on to starting the next step of my original work. However, the research process did
not end there. While analyzing patient files, I encounter medical terminology I am unfamiliar
with and need to complete further research on. In this way, individual research is an ongoing step
in my original work.

Results/Conclusion:
The research process has given me in-depth exposure to topics in immunotherapy, immune
system procedures, and tumor mechanisms that I could not have gained otherwise. I gained
crucial knowledge on how the immune system works by learning about CD8+ and CD4+ T
lymphocytes which are helper T cells that distinguish between self and non-self. The mechanism
by which these helper T cells are able to distinguish between self and non-self antigens includes
the CD4 and CD8 receptors binding to the major histocompatibility complex (MHC) of the target
cell. Another major concept I learned was how tumors are able to surpass such immune
surveillance and keep growing despite the immune system’s regulation. For this, the articles
specified how tumors are able to lose their MHC expression so that helper T cells cannot
recognize them, manipulate the body’s feedback inhibition system to encourage the infiltration
of Treg cells that stop T cell function, and increase expression of immune checkpoint molecules
such as PD-1 and PD-L1 to promote T cell exhaustion. Understanding these mechanisms of
evasion of immune surveillance allowed me to then understand how checkpoint inhibiting drug
work. PD-1 is a protein expressed on the T cell membrane that binds to the PD-L1 ligand which
is expressed on multiple tissue types including tumor cells. This PD-L1 interaction with PD-1
protects the tumor cells for apoptosis and promotes other immunosuppressive activities such as
conversion of T cells in Treg cells. Opdivo and Keytruda stop this PD-1 and PD-L1 interaction
by blocking the reception site of the PD-1 protein. This can increase immune destruction of the
tumor cell, but can also lead to other side effects that I learned from the FDA releases. Such side
effects are scientifically called immune-related adverse events (irAEs) and commonly include
dermatitis, pneumonitis, fatigue, colitis, hypothyroidism, and hypophysitis. After learning all this
information, I scheduled a phone call with my mentor to explain my understanding and clear up
any unclear areas of research. This step of my original work is crucial and promotes constant
learning.

Gathering Patient Data

Objective:
The largest component of any research project is data. Data is what allows researchers to assess
their hypotheses and create further observations. Therefore, the most important part of my
original work is collecting the patient data through analyzing doctor’s notes on the iKnowMed
application. Through gathering data, I hoped to gain familiarity with navigating the common
medical program iKnowMed while finding plentiful information to include in my analysis of
side effects associated with immunotherapeutic drugs. Gathering data is the baseline step of my
original work which will allow me to move farther with my product.

Materials:
● iKnowMed application
● Writing utensil
● Paper for notes

Description of Process:
The essential idea for the data gathering process is to open up the patient files for each individual
that underwent Opdivo or Keytruda therapy and track their response to the drugs over the course
of their treatment. To be successful, Dr. Bhogaraju drew out a chart for me with numerous
parameters that I should include when gathering data. Such parameters were patient ID number,
gender, age, disease, stage of cancer, and treatment. Using a large sheet with the ID numbers of
those who underwent therapy, I need to search up patients one by one and record the basic
information I can find in their files. This basic information includes their age, gender, initials,
and disease which can all be accessed by hovering above the patient’s name in the database.
Next, I need to scroll the patient’s account until I find a section labeled immunotherapy so I can
find their drug type. If I click the drug name, the dosage and dates the patient was given the drug
should appear. Scrolling down, I can see the first day the patient received the drug and use that
information to write the start date for the immunotherapy treatment. After this, I scroll up to the
section labeled office notes. Clicking this tab opens up all the dates that patient visited the clinic
and their doctor’s notes of the key points that took place during the meeting. Using the date
obtained from the immunotherapy section, it is easy to find the doctor’s note from the first day
the patient started their treatment. From there, I need to read each note and write down the
patient’s response to the drug, if they experienced any side effects, and if the drug was
discontinued. I then continue this process for each of the eighty-three patients in the list.
Results/Conclusion:
As I soon discovered, gathering data is a time-consuming process and took me numerous hours
each week over the course of four weeks to complete. This is the bulk of my original work, but
this makes sense as this step of my original work equates to the experiment part of a research
project-- essentially the most crucial aspect. Additionally, as expected with any research project,
I ran into unforeseen obstacles along the way. When completing my patient spreadsheets, I
considered a patient a successful data point when they have undergone multiple doses of their
immunotherapy drugs and clearly responded in a particular way. This made for clear effects that
I could analyze in my final assessment. Unfortunately, a prominent chunk of the data turned out
to be unusable due to the short time frame the patient underwent therapy. A short time frame is
not able to provide an accurate representation of the effects of Opdivo or Keytruda. Additionally,
a couple doctor’s notes were unclear about the effects of the treatment and some did not even
indicate the patient starting the treatment. Despite these faults, the majority of patient cases were
successful data points and provided significant data to assess the side effects of such drugs.

Creating Spreadsheets and Visual Representations

Objective:
The data I collected from iKnowMed is in the format of my own notes-- written for my own
understanding. Now, I need to change this data collecting format into a clean cut and universal
one that will look professional for my final product. Dr. Bhogaraju recommended using Excel to
create a basic spreadsheet to compile the key data from each patient. By completing this step, I
hope to create a data-filled file that Dr. Bhogaraju can look over and check and that I can easily
view to complete my final analysis. Moreover, I plan to create basic charts to highlight certain
patient parameters that will go along with my final analysis.
Materials:
● Microsoft Excel
● Written data gathered from previous steps

Description of Process:
This step is incremental and is completed as I collect data. Each mentor visit, I return with about
fifteen more patient data notes completed to enter into my online spreadsheet. I complete the
parameters of patient ID, gender, age, disease, treatment, duration of treatment, response (Yes or
No), side effects (Yes or No), prescriptions to side effects, and discontinuity. At the end of each
patient row, I create a review note with additional information I hope to include. I highlight any
rows light green if I have missing data that I cannot find from my notes and need to go back to
review. Additionally, I highlight any row light red if I believe there is not enough data for the
patient to be considered a valid data point. Then, when I go back for another mentor visit, Dr.
Bhogaraju checks the work I did so far and tells me if any of the side effects I noted are not
actually associated with checkpoint inhibiting drugs. For the visual representation aspect of my
original work, I need to find trends in my data much like last year to create charts such as age vs.
discontinuity.

Results/Conclusion:
Completing this step of my original work created insurance just in case I cannot find my original
notes. In addition, creating spreadsheets allows for me to compile my diverse data into an unified
format for me to use for further analysis and my final product. It also provided a platform for my
mentor to keep up with my original work and check over my progress. Although I have not
started the visual representation aspect of this step yet, I know it too will allow me to further
general understanding of my data.

Analysing the Data

Objective:
As mentioned in the last step, I need to complete visual representations finding patterns within
my data to include in my analysis. In order to complete this step, I need to decide which factors
of the patient have connections with the side effects they experienced and response to the drugs.
Additionally, before I can move on to write my final report of my findings, I need to understand
which side effects showed up commonly and if any patient parameters corresponded to it.
Finally, I will need to analyze if my finding supports the research of clinical trials performed by
other institutions. Completing this step is the key to writing my medical paper.

Materials:
● Notes from gathering data

Description of Process:
I do not plan to follow my data analyzing steps from last year and heavily rely on statistical
modeling tools such as R Programming Studio and Matlab. This is due to the fact that my data
this year is mostly qualitative rather than quantitative like last year. Instead, the most obvious
way to go about finding trends in my data is by using my spreadsheets to find points to focus in
on. I first will look at the side effects experienced column of spreadsheet and count the
occurrences of each type of irAE. I will then notice the disease, treatment, treatment duration,
and other parameters to find if any data is frequent among the patients.

Results/Conclusion:
I have not fully completed this step of my original work as I need to complete gathering all my
data before moving on to this step. However, even with the data I have so far, I am able to
already see trends in the patients. I noticed that most patients do not experience side effects as
should be expected due to the popularity of this drug type. Those that do experience irAE mostly
develop dermatitis such as skin rashes which are commonly treated with corticosteroid creams.
Dermatitis related side effects usually develop near the start of the therapy but are easily treated.
Still, most immunotherapies are discontinued due to the failure of stabilizing the disease.

Compiling Data into Medical Analysis Paper

Objective:
The point of my original work this year is so I can gain knowledge about the clinical research
process. The largest part of any research project is the conclusion and final learnings. For me to
duplicate this portion of the research process, I will be creating the final paper detailing my
findings from this study. I hope to parallel the professional clinical study result papers I read for
research assessments with this final step of my original work.
Materials:
● Microsoft Word
● Portfolio

Description of Process:
Dr. Bhogaraju and I decided that this step of my original work should start right after I finish
compiling the patient data. By this timeline, I hope to discuss with Dr. Bhogaraju on April 12 on
how to proceed with my medical analysis paper. I plan on obtaining examples of clinical studies
from Dr. Bhogaraju to create my own. I will then compile all the information I gained from my
original work into a professional paper written in the format Dr. Bhogaraju provides. In
completing the final product, I hope to add my original patient notes, spreadsheets, and visual
representations to my written work to create one portfolio for final presentation night. However,
the highlight of the portfolio will be the written component.

Results/Conclusion:
I haven’t yet completed this step of my original work, but I will consider it a success if I gain a
better understanding of how to display results in a matter seen in the medical field. I also hope
my research portfolio displays a level of quality similar to that of the research I read on
uptodate.com.

ISM S.M.A.R.T Goals Progress:

When creating my S.M.A.R.T goals presentation for this year I included many personal
goals as well as goals specific to ISM. My ISM goals included reading two chapters of Cancer:
An Emperor of All Maladies per week, changing my site domain, and obtaining ten subscriptions
of oncology website. My personal goals were to read three books every month, learn a new piano
song every month, and to dedicate more time to do activities I enjoy. Unfortunately, I was unable
to follow with my ISM goals due to changing my original work idea from creating a website to
helping with clinical research. With this, the goals of changing my website domain and obtaining
subscriptions would be pointless to complete. However, I did combine my goal of reading
Cancer: An Emperor of All Maladies with my personal goal of reading three books per month
and was able to complete it in a few sittings. As for my personal goals, I was able to follow
through with them better. I have been making frequent trips to the library to get books with my
family. Along with my books, I make the effort of finding one non-fiction book to increase my
knowledge. With this, I have been able to learn about Spanish, European History and the
periodic table during the first three months of the year. I have also been wasting less time on
social media which cleared up my schedule and allowed me more time to comfortability
complete my homework and get ahead on my work. This in turn greatly reduced my stress levels
and allowed me time to do the things I actually enjoy and was not able to pursue during my high
school experience. I have been playing piano more and exploring creative aspects of life such as
photography and bullet journaling. I have also been trying to spend more time with my sister and
family before I go away to college. I am actually amazed to find a drastic difference in my
lifestyle and in turn my stress levels. With virtually minimal stress, I am much happier than I
have ever been in high school and feel like a more positive person. I know that not
procrastinating is heavily emphasized by teachers, but quite hard to actually do. I never expected
such a difference in my mental health by not procrastinating and pursuing my interests. Overall, I
am very happy with my results from following my personal S.M.A.R.T goals and plan to
continue for the future.