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Shelby Hall

DOS 711 Research Methodology

Identifying Gaps in Literature

Article 1

In the article titled “Post-Mastectomy Radiation Therapy (PMRT) and Two-Staged Implant-
Based Breast Reconstruction: Is There a Better Time to Radiate?” the authors discuss whether
the timing of radiation has an impact on postoperative complication rates. They evaluated
patients who received radiation following tissue expander placement versus those who received
radiation after the exchange for a permanent implant. This five-year prospective, multi-
institution study found 150 patients that underwent two-staged implant-based breast
reconstruction. Overall, the study found that there were no differences, between the two types of
patients, in the incidence of complications, or complications leading to reconstructive failure.
The authors do mention that there is conflicting data out there regarding this topic. They also
suggested that there are areas of the topic that aren’t covered in this research and should be
researched further.1

A future research project regarding this topic would focus on a much larger number of patients in
the study in order to strengthen any findings. This study would also evaluate complication rates
between the differing patients, but it would include more information regarding the exact timing
between radiation and the surgical procedures themselves. The follow-up period for each patient
would also need to be extended from six months. This would allow for more evaluation of any
long-term complications that could arise such as reconstructive failure down the road.

Problem Statement: Post-mastectomy radiation therapy is a vital part of breast cancer


treatment. In these cases, the patients are at a higher risk of recurrence and radiation can reduce
those risks. Following mastectomy, many patients opt for reconstruction that can be done in two
stages. The effects of radiation in the setting of reconstruction are not yet fully understood.

Purpose: To evaluate short-term and long-term complication rates based on the timing of
radiation for patients with tissue expanders versus patients with permanent implants at the time
of radiation.
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Article 2

In the article titled “Liver Reirradiation for Patients with Hepatocellular carcinoma and liver
metastasis” the authors discuss the safety and efficacy of liver reirradiation. In the past,
reirradiation of the liver was limited because of the risk of radiation-induced liver disease. In this
retrospective study, they looked at a total of 49 patients who had been treated at their institution
and received a second course of radiation to the liver. This second course could be to the same
tumor, a different tumor, or a combination of the two. The average prescription dose was similar
between the initial and the retreatment, but the treatment volumes were often smaller for the
retreatment. Of the 49 patients, only 2 showed signs of nonclassic radiation-induced liver
disease. The authors made several recommendations when it comes to the dose to the nontarget
liver, as well as the volume of unirradiated liver. They did conclude that liver reirradiation may
be a safe, tolerated option, but that further research is needed to establish the safety and
efficacy.2

For this topic, there needs to be more prospective studies done regarding reirradiation of the
liver. A potential study would have a larger population of patients based on eligibility criteria.
The radiation dosing and techniques could also be more uniform to gather more homogeneous
data. The time between treatments would be taken into account in order to assess the previous
doses and to determine the retreatment dose. This study would allow for a more thorough
evaluation of toxicities from the retreatment.

Problem Statement: Hepatocellular carcinoma commonly spreads throughout the liver, which
leads to the potential for multiple courses of radiation. The liver is also a common location for
metastasis, which can also lead to more radiation. The safety of liver reirradiation needs to be
further examined in order to determine dose and technique limitations.

Purpose: To determine safe tolerances associated with reirradiation of the liver.

Article 3

The article, “Re-irradiation in lung disease by SBRT: a retrospective, single institutional study”
evaluates the outcomes of using SBRT for re-irradiation for lung disease by assessing local
control and toxicities. As stated in the title, this was a retrospective study with a total of 22
patients and a total of 27 lesions treated. The median time between the initial treatment and the
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retreatment was 18 months. Majority of the patients received their retreatment over several
fractions versus one treatment. The results showed that local control had been reached at 1-2
years for 18 out of the 27 re-irradiated lesions. Overall, the treatment was tolerated well. They
concluded that SBRT may offer a curative treatment for recurrent lung disease. Similar to the
previous article, the authors stated that further research should be conducted to obtain optimal
results.3

A future study regarding this topic would be a prospective study with a larger patient population.
A longer follow-up time period is also key in determining short and long-term toxicities and
local control. Keeping the treatment technique the same, can help evaluate the data in order to
come to a solid conclusion.

Problem: Lung cancer is one of the leading causes of cancer-associated death. Whether
discussing primary lung cancer, or lung metastasis, the probability of secondary lung tumors is
relatively high. This leads to the need for more treatment, particularly re-irradiation.

Purpose Statement: To determine the best candidates for re-irradiation of lung recurrence using
SBRT by evaluating local control, toxicities, and overall survival.

Article 4

In the next article titled, “Carbon Fiducial Image Guidance Increases the Accuracy of
Lumpectomy Cavity Localization in Radiation Therapy for Breast Cancer” the authors set out to
explore the feasibility and potential accuracy of utilizing carbon fiducials to locate the
lumpectomy cavity with KV imaging. There were 11 patients in this study, and 9 of them
received whole breast irradiation with lumpectomy boost while the other two received partial
breast irradiation. The article discussed the use of carbon fiducials with proton and photon
therapy. In proton therapy, the use of surgical or gold markers isn’t ideal because of metal
artifact and uncertainties in interactions with the beam. These carbon fiducials have shown to be
a suitable alternative in some studies regarding prostate localization. To evaluate their use in
breast cases, they compared setup errors between different methods of target localization.
Another factor that came into play was whether the patient was free breathing or utilizing deep
inspiration breath hold (DIBH) and the effect that has on setup errors. On CBCT and KV
imaging, the carbon fiducials were easily visible and showed minimal artifact. They concluded
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that carbon fiducial localization using KV imaging had better accuracy then the other methods
they utilized. Another topic they discuss is the fact that these fiducials have the potential to
migrate, which could throw off the localization. In the end, they state the using these fiducials
can result in about a 4mm reduction in PTV margin.4

A future study that is suggested looks at the differences in setup error when comparing a free
breathing treatment to a DIBH treatment. Instead of looking at the known advantages, like heart
and lung dose, we would evaluate the potential reduction of setup uncertainties or errors when
using DIBH. While there are a few studies regarding this showing minimal differences, a study
with a larger population of patients would further investigate the topic.

Problem Statement: In Radiation Oncology, the ideal treatment has minimal dose to the normal
tissues. In order to accomplish that we need to evaluate ways to reduce our target volumes in
ways that don’t compromise target coverage. Setup uncertainties lead to larger margins. How can
we reduce this uncertainty?

Purpose: To evaluate the impact of DIBH versus free breathing treatments on setup
errors/uncertainties.

Article 5

The last article is titled “Definitive Local Therapy is Associated with Improved Overall Survival
in Metastatic Cervical Cancer.” This study compared the use of definitive local therapy versus
conservative therapy. Definitive local therapy is either concurrent chemoradiation or definitive
surgery. Conservative therapy is systemic therapy with or without palliative radiation. The
potential benefits of utilizing definitive local therapy haven’t been fully investigated, so the
authors hypothesized that the overall survival would be greater with definitive local therapy. This
large study included 2,838 patients from the National Cancer Database. The results showed
improved overall survival with definitive local therapy as hypothesized, with a median overall
survival of 19.2 months versus 10.1 months with conservative therapy. While overall survival is
an important piece in determining which therapy is best for a patient, there are also other factors
that need to be considered. Another important endpoint they suggested looking at was quality of
life.5
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A similarly-structured future study could evaluate the impact of this more aggressive definitive
local therapy on a patient’s quality of life in comparison with the conservative therapy. It is
obviously important to study overall survival for different treatments, but we also need to know
how the patient tolerates treatment and how it affects their quality of life.

Problem Statement: Cervical cancer affects many women each year, approximately 14% of
cases present with distant metastatic disease at diagnosis.5 Systemic therapy on its own hasn’t
shown significant improvement in local control. While definitive local therapy might offer more
local control and improve overall survival, what is the impact on the patient’s quality of life?

Purpose: To evaluate the impact of utilizing definitive local therapy in metastatic cervical
cancer on a patient’s quality of life.
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References.

1. Santosa KB, Chen X, Qi J, et al. Post-mastectomy radiation therapy (PMRT) and two-staged
implant-based breast reconstruction: is there a better time to radiate. Plast Recontr Surg.
October 2016;138(4):716-769. doi:10.1097/PRS.0000000000002534
2. McDuff SG, Remillard KA, Zheng H, et al. Liver reirradiation for patients with
hepatocellular carcinoma and liver metastasis. Pract Radiat Oncol. 2018:8(6):414-421.
https://doi.org/10.1016/j.prro.2018.04.012
3. Caivano D, Valeriani M, De Matteis S, et al. Re-irradiation in lung disease by SBRT: a
retrospective, single institutional study. Radiat Oncol. 2018;13(1):87.
https://doi.org/10.1186/s13014-018-1041-y
4. Zhang Y, Mutter RW, Park SS, et al. Carbon fiducial image guidance increases the accuracy
of lumpectomy cavity localization in radiation therapy for breast cancer. Pract Radiat Oncol.
2019;9(1):e14-e21. https://doi.org/10.1016/j.prro.2018.09.006
5. Venigalla S, Guttmann DM, Horne ZD, et al. Definitive local therapy is associated with
improved overall survival in metastatic cervical cancer. Pract Radiat Oncol. 2018;8(6):e377-
e385. https://doi.org/10.1016/j.prro.2018.05.010