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Article Analysis Part 1: Trade Magazine

An article in a peer-reviewed journal is exactly as described. Said article must be

approved by reviewers within the field before it can be published. Peer-reviewed journal articles
are written by experts in their field and are geared toward being non-biased, both with the use of
blinded studies and a lack of prejudiced financial backing.1 Conversely, articles available in trade
publications are not vetted through a peer-reviewed process. Their target is not limited to experts
within the field, but rather speak to a wide audience. They are also typically free for anyone to
access, due to their financial backing from advertisers. After examination of a trade publication
and a peer-reviewed journal, the previously notated differences, among others, are apparent. This
part of the analysis will focus on an article written by Kaiser2 titled “Modified T Cells that
Attack Leukemia Become First Gene Therapy Approved in the United States.” This article was
published in the trade magazine Science and is available online through the Science magazine
website. The subsequent analysis will provide a brief summary of the article, and will address its
strengths, weaknesses, and perceived usefulness.

Kaiser2 focuses on a form of gene therapy developed by Novaris, called Kymriah. She
emphasizes that it is the first gene therapy to be approved by the FDA and provides a brief
explanation of what the treatment involves, which is the modification of T-cells to target acute
lymphocytic leukemia (ALL). The author highlights some of Novaris’ clinic trial data, including
that 83% of the 63 patients with B cell ALL achieved remission during the trial. Kaiser2 reports
that after a unanimous vote from an advisory panel, the FDA has approved this treatment for
children and adults up to 25, diagnosed with B cell ALL, with a lack of response to conventional
therapy or for those who have relapsed. The author mentions that, though there is positivity
surrounding the modified cells, called CAR-T cells, there are also elements of concern. Among
those listed include the cost of the drug being $475,000, and the reports of shortages at some
medical centers during the trial phase. Kaiser2 mentions the current gene therapy market in
Europe and concludes with a reference to the potential FDA approval of a gene therapy for
lymphoma within the subsequent year.

Given the sources provided by the author, it is reasonable to have doubt regarding the
reliability of every detail presented. The article does have a basis in fact. The drug and trial
information can be found by researching the FDA3, but the provided details do not have strong
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supportive sources. The author provides no formal reference list in this online copy of the article.
She does link certain sections of the article to other articles posted in various sources, but the
reliability of said sources are not known. The author herself is a staff writer for Science
magazine, a reporter, rather than an expert on this topic, and there is no way to know if the article
was fact checked by someone other than the author herself. There is also the possibility that the
article could have been influenced by someone with bias toward Novaris. Based on the content
this seems unlikely, but there is no affiliation provided, so the possibility cannot be firmly ruled
out.

The strength that is the easiest to identify in this article is the one that it shares with most
trade magazine publications.1 It was not grossly technical, easy to read, and wasn’t so long as to
be a chore. In addition, the author not only provided general information and the positive aspects
regarding this gene therapy, but also referenced potential concerns. The chief weakness of this
article is, as mentioned, its lack of supportive sources, and thus the potential for accuracy
concerns. In addition, the author fails to support some of the claims in the article. An example
would be when the author states that “most ALL patients respond to standard therapy,”2 without
providing any data or sources to support this claim.

Science magazine caters to a wide audience, as do most trade magazines.1 The website
for the magazine is attractive to the eye, and every article has a picture and a large title. Within
the article there are bolded sections of sentences, better to catch the eye of a person skimming.
Regarding application to a professional in the field of dosimetry, the article does not have
clinical relevance. This is to be expected because trade publications are typically not targeting a
single profession. The article could be of interest to others, as it was to me, because of its updates
regarding new cancer treatments. It is also not entirely irrelevant, because immunotherapy is
becoming a larger player in the treatment of cancer. For example, we use a protocol in my clinic
that requires the treatment of pediatric primary brain tumors with a lower than standard dose of
radiation in order to activate the immune response prompted by the immunotherapy drug
Indoximod, which is given in combination with chemo.

The trade article offered interesting news regarding the approval of a gene therapy
treatment. It was easy to read, and offered positive and negative details, but lacked supportive
sources and failed to fully back some of the claims therein. Although the article does not provide
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clinically relevant data, it does offer interesting updates about developments in other fields that
may intertwine or relate to the patients that we treat. One should just remember that the details
within are only as good as their sources.
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References

1. Lenards N, Weege M. Reading and Writing in Radiation Therapy & Medical Dosimetry.
[SoftChalk]. La Crosse, WI: UW-L Medical Dosimetry Program; 2016.
2. Kaiser J. (2017, August 30). Modified T cells that attack leukemia become first gene therapy
approved in the United States. Science, (356), 122. Retrieved from
http://www.sciencemag.org/news/2017/08/modified-t-cells-attack-leukemia-become-first-gene-
therapy-approved-united-states.
3. United States Food and Drug Administration. Approved Products: Kymriah (tisagenlecleucel).
https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/
ucm573706.htm. Updated August 27, 2017. Accessed January 30, 2018.
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Article Analysis Part 2: Professional Journal

For the second part of this analysis I chose to examine the International Journal of
Radiation Oncology, Biology, and Physics. This journal publishes peer-reviewed research related
to radiation oncology, radiation biology, and medical physics, along with policy as it relates to
the field. I selected the article “Dosimetric Comparison of Three-Dimensional Conformal Proton
Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for
Treatment of Pediatric Craniopharyngiomas”, authored by Boehling et al,1 for further
examination. The article, in the fashion of most peer-reviewed publications, has a structured
format, and includes a sufficient list of reputable sources.2 Unlike many trade publications, this
article also contains extensive data tables, isodose distribution figures, and graphs. The
subsequent analysis will discuss the aim of the research, the methodology, the results, and my
summative impression.

Boehling et al1 presents an implied research question regarding the dosimetric reduction
in integral dose to normal tissues with the use of a 3D-PRT or IMPT plan, as compared to an
IMRT plan, for the treatment of pediatric craniopharyngiomas. The researchers sought to
compare plans from the three modalities in order to quantify the level of integral dose reduction
to normal tissues that 3D-PRT and IMPT provide, as compared to IMRT, for this particular
malignancy. The authors gave adequate background on craniopharyngiomas, their typical
treatment regiments, and the criticality of their location due to their close proximity to multiple
vital structures. After citing sources that support the efficiency of proton treatment for
craniopharyngiomas, and acknowledging the recognized potential that protons have for sparing
tissue, the authors presented a lack of dosimetric comparison data as justification for this
research. The authors support the relevance of this research by citing information regarding the
importance of normal tissue sparing in pediatric patients, and by presenting sources that focus on
the high sensitivity to irradiation of neuronal stem cells, which are located in areas that are in
close proximity to craniopharyngiomas.

Boehling et al1 selected 10 pediatric patients treated at the University of Texas M.D.
Anderson Cancer Center Proton Therapy Center. This sample is small, which should be taken
into consideration, but it is also important to note that recent epidemiological data suggests
incidence rates of only 129-152 cases per year.3 Thus, sample size was most likely limited by the
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number of craniopharyngioma patients available for comparison. Simulation CT data was fused
with corresponding T1-weighted MRI’s for all patients.1 Contouring was performed using the
Varian Eclipse planning system, and the authors designated uniform standards for organ at risk
(OAR) contours and gross tumor volume (GTV) expansion. Planning was executed by
dosimetrists and physicists who had experience with 3D-PRT, IMPT, and IMRT planning. The
authors set standard planning guidelines for each modality. Boehling et al1 describe the measures
used in evaluating target coverage, conformation, dose distribution, and the separate measures
used in the evaluation of OAR sparing. The authors also provide their method for statistical
analysis.

Boehling et al1 report no significant differences in target coverage for the three
modalities. The authors found that the IMPT plans produced large decreases in integral dose, in
comparison to the IMRT plans, for all OAR’s examined. Organs included the hippocampus,
dentate gyrus, subventricular zone, cerebral vasculature, infratentorial and supratentorial brain,
and the brainstem. The 3D-PRT plans produced decreases in integral dose, in comparison to the
IMRT plans, for all organs except the subventricular zone. The authors surmise that this lack of
sparing of the subventricular zone is due to the intersection of the lateral vertex beams. Boehling
et al were able to conclude from the acquired data that proton therapy plans produced significant
reduction in dose to normal tissues at both low and high dose levels. Based on their data, the
authors surmise that proton therapy would translate into diminished late effects, especially in
regard to the incidence of ischemic events. They do recognize that this is impossible to say for
certain without clinical trial data and long-term evaluation.

I found this study to be interesting in terms of being able to examine plan data from
different modalities all performed on the same patient. This allows full appreciation of the
differences in coverage and OAR sparing in a controlled format. I have seen examples of proton
isodose configurations and have read information regarding the therapies potential for organ
sparing, but this data provides a concrete comparison. The small sample size could be considered
a limitation,2 but size was likely restricted due to the sheer rarity of this disease. I consider the
fact that the authors did not take the potential effects of secondary neutron dose into
consideration1 to be a definite limitation, even though they cited a study that found neutron
exposure produced lower risk of secondary malignancy than IMRT.
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After fully reviewing both articles presented in this analysis, the differences in their
presentation and in their provided information are quite clear. Though the articles were not on
the same topic, it is still possible to evaluate the differences in their content. The focus of the
peer-reviewed article by Boehling et al1 was producing data to establish dosimetric evidence
regarding the OAR sparing potential of proton therapy, as compared to IMRT, for the treatment
of pediatric craniopharyngiomas. The format was structured, with an established purpose and a
justification for the research. This is in steep contrast to the style of the trade article, which
presented a general and easy to read overview of a gene therapy treatment for ALL. Another key
difference was that the peer-reviewed article had 50 sources, while the trade article had next to
none. While both articles presented interesting information, the trade article was merely useful in
terms of providing a general update on a topic, whereas the peer-reviewed article provided
information that is clinically relevant for radiation oncology professionals.
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References
1. Boehling NS, Grosshans DR, Bluett JB, et al. Dosimetric comparison of three-dimensional
conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated
radiotherapy for treatment of pediatric craniopharyngiomas. International Journal of Radiation
Oncology, Biology, Physics. 2012;82(2):643-652. doi:10.1016/j.ijrobp.2010.11.027.
2. Lenards N, Weege M. Reading and Writing in Radiation Therapy & Medical Dosimetry.
[SoftChalk]. La Crosse, WI: UW-L Medical Dosimetry Program; 2016.
3. Larkin S, Karavitaki N. Recent advances in molecular pathology of craniopharyngioma.
F1000Research. 2017;6:1202. doi:10.12688/f1000research.11549.1.