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Makelle Barski
April 2, 1019
DOS 711 Research I
Identifying Gaps in Literature
Article 1: Effects of multiple breath hold reproducibility on treatment localization and dosimetric
accuracy in radiotherapy of left-sided breast cancer with voluntary deep inspiration breath hold
technique
The article, “Effects of multiple breath hold reproducibility on treatment localization and
dosimetric accuracy in radiotherapy of left-sided breast cancer with voluntary deep inspiration
breath hold technique” by Kapanen et al1 discusses breath hold reproducibility for left sided
breast cancer patients. The study investigated patients that had whole breast radiation with 3-5
breath holds and patients with whole breast and supraclavicular nodes with 7-9 breath holds.
Setup and field images of the chest wall and clavicle were obtained to analyze interfractional and
intrafractional positional errors. The results concluded that on average, the set up error superiorly
was 1.4 mm, inferiorly 1.9 mm, and 1.2 mm anteriorly and laterally. Longitudinally, the setup
error was larger, with the error being at least 2 mm for 38% of patients receiving whole breast
and supraclavicular radiation. These errors caused dosimetric error from 8.3% to 10.1%. The
study stated that the larger amount of error was due to more breath holds.
The author of this article never stated that reproducibility and accuracy are different. The
author’s findings did not assess reproducibility. The study took the average of the setup errors
instead of comparing it with a standard. The sample size was very small with 20 whole breast
patients and 27 whole breast and supraclavicular nodes. In future studies on the same topic, it
should be individual based. During treatment, patients go up for multiple breath holds and every
breath hold is slightly different, so a port film can be taken (by interrupting the beam) on each
breath hold. There should be multiple port films taken during each fraction to get more accurate
results, not just one on the first breath hold. These suggestions could be used to make this study
more accurate and better discuss reproducibility.
Article 2: Immobilization and image-guidance methods for radiation therapy of limb extremity
soft tissue sarcomas: Results of a multi-institutional survey
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The article, “Immobilization and image-guidance methods for radiation therapy of limb
extremity soft tissue sarcomas: Results of a multi-institutional survey” by Swinscoe JA, Dickie
CI, Ireland RH2 discusses how patient positioning in radiation therapy is challenging for limb
extremities in soft tissue sarcomas. It mentions that cases like these require accurate,
reproducible dose delivery. The study was a survey, with the sample of 73 UK radiation therapy
centers and 15 hospitals in 7 other countries. The information that was surveyed was regarding
immobilization devices used, patient setup tolerances, written protocols, the modality and
frequency of image guidance, treatment methods and times, and if there were use of surgical
clips. The results of immobilization used can be summarized by looking at the chart below:

Device 73 UK centers 15 International centers

Lower
limb, Upper limb, n Lower limb, Upper limb, n
n (%) (%) n (%) (%)

Thermoplasti 38 (52) 38 (52) 7 (47) 6 (40)

c

Perspex 8 (11) 10 (14) 0 (0) 0 (0)

shell
Vacuum bag 56 (77) 41 (56) 11 (73) 12 (80)

Bolus bag 7 (10) 6 (8) 0 (0) 1 (7)

Foot rest 36 (49) 10 (14) 1 (7) 1 (7)

Ankle 26 (36) 1 (1) 2 (13) 1 (7)

support
Hand grips 1 (1) 13 (18) 2 (13) 2 (13)
Others 17 (23) 25 (34) 7 (47) 7 (47)

In regards to setup tolerance results, 60% of UK clinics have a tolerance of 5 mm and

15% have 3 mm for upper and lower extremities. Internationally, 3-5 mm were the most common
tolerances. In regards to written protocols, UK centers had 29% use protocols for for lower limb
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and 18% for upper limb. Internationally, 47% used protocols for upper and lower extremities.
Overall, appointment times varied from 10 to 30 minutes with multiple forms of treatment such
as conventional, IMRT, of VMAT. In regards to imaging, UK used kV daily 12% of the time,
37% for the first three fractions followed by weekly imaging. MV had similar percentages.
Internationally, 33% used kV daily with 20% using imaging for the first 3 fractions followed by
weekly imaging. MV had one center using it daily and 13% used it in the first 3 fractions
followed by weekly imaging. CBCT was the most commonly used, with 40% using it daily and
13% using it the first three fractions followed by weekly imaging. In regards to surgical clips,
approximately 25% of UK centers used surgical clips and 53% of the international clinics used
surgical clips.
This study was limited because it was only a survey. Surveys are like a screenshot in that
time and place, and radiation therapy departments are constantly changing so the information
collected and results found are constantly changing. The study stated that when departments
stated they used multiple immobilization devices it was not possible to know if device were used
in combination or selected from available immobilization use per each individual, making the
survey flawed. Also, to call this study international is technically correct, however, 83% of the
countries were UK, so it was flawed because it was so heavily based on UK clinics. This study
measured multiple variables, which is good because it gave a lot of information, however, some
variables were emphasized more than others. I believe if you are going to measure multiple
variables, they should be equally measured and not one more than another. Also, the opening
lines of this article stated how important reproducibility was in regards to soft tissue sarcomas
extremities. The article then never mentions how the results are related to reproducibility. If I
was to conduct further research on this topic, I would measure the shifts needed daily using
CBCT based on the immobilization used and this would suggest the best methods to use to
achieve the ultimate goal of reproducibility.
Article 3: Risk of dry eye syndrome in patients treated with whole-brain radiotherapy
The article “Risk of dry eye syndrome in patients treated with whole-brain radiotherapy”
by Nanda et al3 discusses how patients that receive whole brain radiation are starting to live
longer and therefore see the effects of dry eye. Usually the lacrimal gland’s dose is not taken into
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consideration when planning or treating the patient. This study looked at 70 3D plans with 36
plans having a fractionation of 30 Gy/10 fx, and 34 plans with a fractionation of 37.5 Gy/15 fx.
The lacrimal glands were then contoured and biological effective dose maximum constraints
were calculated to be 32.17 Gy for 30 Gy and 36.70 Gy. The mean dose for the 30 Gy plans were
2.5 Gy and for the 37.5 Gy plan was 35.2 Gy. BED was violated for the 30 Gy prescription in
61.5% of patients when supraorbital blocking was bordering the supraorbital ridge (T1), 46.4%
when blocking had no contact with supraorbital ridge (T2), and 27.8% when blocking covered
the supraorbital ridge (T3). And for the 37.5 Gy patients it was violated 100% of the time for all
of the blocking types stated above. When looking at the results, the 30 Gy fractionation has a
lower BED on the lacrimal gland as well as the T3 technique.
The study did a great job of identifying a problem, and quantifying the doses to the
lacrimal gland and identifying a solution. The study actually identified further research needed
by stating that further trials should evaluate the lacrimal gland toxicity on a follow up. Also, a
lacrimal avoidance study could be done and a follow up evaluation could be done to compare.
Further studies could be other structures in or near the brain that are causing complications on
follow up evaluations. Hippocampal sparing is becoming more prevalent in whole brain radiation
therapy (WBRT); so there is becoming a trend in sparing tissues in WBRT and further research
on those tissues could be done just like this lacrimal gland study.
Article #4: Is It Necessary to Test Oropharyngeal Cancer for Both p16 and Human
Papillomavirus?
The article “Is It Necessary to Test Oropharyngeal Cancer for Both p16 and Human
Papillomavirus?” by Deraniyagala4 discusses a purpose to test for p16 and HPV in patients with
oropharyngeal cancer based on another article that suggested low-dose elective nodal irradiation
for patients wit oropharyngeal with HPV. The article implies that those with and without HPV
will have a different course of radiation, so it would be important to test HPV. Currently, HPV
testing is not routinely tested due to insurance programs. An informal survey was done asking
10 colleagues that specialize in head and neck cancers if p16 and HPV testing should be done
and about half said they do not test for it and the other half stated they attempt to test for it but
financial reasons make it unsuccessful most of the time. The author concludes that the testing is
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not necessary because evidence based data is lacked. The author states his opinion that if it
changes the course of radiation, that it should be tested for; however, because evidence is not
strong enough to support this claim, the author does not change treatment off-protocol and does
not request a test.
HPV and its link to cancer is relatively new, especially with its link to oropharyngeal
cancer. The whole article states how there is lack of evidence based on HPV testing in
oropharyngeal testing and therefore the radiation treatment used for HPV. The article is very
informal and states that there is a need for more evidence. Further research needs to be done on
HPV testing and oropharyngeal cancer. A more quantitive study on how many patients have HPV
and also a study on the different treatment techniques need to happen. When these studies are
done and more evidence based on this subject become apparent, insurance companies policies
about HPV testing will have to evolve to test these patients so that the patient can receive a better
radiation treatment.
Article #5: Real-time Online Matching in High Dose-per-Fraction Treatments: Do Radiation
Therapists Perform as Well as Physicians?
The article “Real-time Online Matching in High Dose-per-Fraction Treatments: Do
Radiation Therapists Perform as Well as Physicians?” by Levin et al5 discusses how physicians
typically do CBCT matching pretreatment. The study investigated whether radiation therapists
(RTT) were as qualified as physicians in matching. 16 RTTs and 5 doctors participated, aligning
CBCT on 113 patients with a total of 324 measurements with soft tissue tumors. It resulted in no
significant difference so the take away is that RTTs are qualified to align cone beam prior to
treatment and physicians can check it after.
This article was a great study to change a policy within a department to make it more
efficient. I think the sample size was very small and that multiple departments should have been
in this study, and not just the one. In a future study, I would make my sample size even larger and
also include physicists, because they align CBCT in some radiation therapy departments. Also,
the physicians and therapist did not all have the same amount of CBCT to align to, which could
be a problem because some physicians and therapists may be better than others or the opposite,
so the results may be skewed. These are changes that could be made for further research.
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References
1. Kapanen M, Laaksomaa M, Pehkonen J, et al. Effects of multiple breath hold reproducibility
on treatment localization and dosimetric accuracy in radiotherapy of left-sided breast cancer
with voluntary deep inspiration breath hold technique. Medical Dosimetry. 2017;42(3):
177-184. doi:10.1016/j.meddos.2017.02.004.
2. Swinscoe JA, Dickie CI, Ireland RH. Immobilization and image-guidance methods for
radiation therapy of limb extremity soft tissue sarcomas: Results of a multi-institutional
survey. Medical Dosimetry. 2018;43(4):377-382. doi:10.1016/j.meddos.2017.12.003.
3. Nanda T, Wu C-C, Campbell AA, et al. Risk of dry eye syndrome in patients treated with
whole-brain radiotherapy. Medical Dosimetry. 2017;42(4):357-362. doi:10.1016/j.meddos.
2017.07.007.
4. Deraniyagala R. Is It Necessary to Test Oropharyngeal Cancer for Both p16 and Human
Papillomavirus? Practical Radiation Oncology. 2019;9(2):61-62. doi:10.1016/j.prro.
2018.10.014.
5. Levin D, Grinfeld G, Greenberg V, et al. Real-time Online Matching in High Dose-per-
Fraction Treatments: Do Radiation Therapists Perform as Well as Physicians? Practical
Radiation Oncology. 2019;9(2). doi:10.1016/j.prro.2018.10.002.