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Identifying gaps in literature and future research

Article 1

Three-Dimensional Bioabsorbable Tissue Marker Placement is Associated with Decreased

Tumor Bed Volume Among Patients Receiving Radiation Therapy for Breast Cancer1


This retrospective case-control research studied breast cancer patients treated at a single
institution between 2015 and 2016. The aim was to determine if 3-dimensional bioabsorbable
markers improved tumor bed delineation, with the hypothesis that “3-dimensional bioabsorbable
marker placement would lead to detectable differences in TBV delineation”1. A selection of the
patients were implanted with a 3-dimensional bioabsorbable marker into the tumor bed at the
time of surgery, whereas the remainder had their tumor beds delineated by traditional methods
such as use of surgical clips or visualization of post-operative changes in tissue on CT. The
resultant volumes, tumor bed volume (TBV - bioabsorbable marker) and tumor excision volume
(TEV - traditional methods), were compared. The statistically significant results showed that the
TBV volumes were, on average, smaller than the TEV volumes.1

Future research:

The above research suggests that smaller tumor bed boost CTV volumes may result in lower
toxicity profiles, but acknowledges that multi-center trials need to be performed in order to
assess the long-term effects of smaller boost volumes on cardiac, lung, and skin toxicities, as
well as local control.1 In the absence of data for long-term follow up on patients receiving
bioabsorbable markers at the time of surgery for breast cancer, a prospective multi-center trial
would randomize patients to either implant of a bioabsorbable marker, or no surgical delineation
of tumor bed, and collect data on OAR doses, acute and long-term reported toxicities, and long-
term local control. This data would be analyzed in order to assess the efficacy of reduced tumor
bed CTV volumes aided by the use of a 3D bioabsorbable marker.

Article 2

Less Than Whole Uterus Irradiation for Locally Advanced Cervical Cancer Maintains
Locoregional Control and Decreases Radiation Dose to Bowel2


This study aimed to provide justification for an institutional practice of undercontouring the
uterus in irradiation for patients with locally advanced cervical cancer. Fifty-three patients from a
single institution were retrospectively reviewed and data obtained for dosimetric parameters such
as the GTV volume, the volume of uterus included in the PTV, the mean dose to the uterus,
bowel doses, and local/regional/distant failures. With a 44-month follow up, they found that no
patients had isolated local recurrence, and the 2-year loco-regional failure rate was 10.9%. The
median volume of uterus included in the PTV was 66%, and those patients with less than 90% of
the uterus within the PTV experienced significantly lower bowel doses, although lower bowel
toxicity was not confirmed clinically.2

Future research:

A multi-center prospective randomized clinical trial should compare traditional cervical CTV
volumes (including the entire uterus) with less-than-whole-uterus volumes. With the hypothesis
that the latter, smaller volume decreases the amount of bowel-related adverse events without
compromising loco-regional failure rates, patients would need to undergo long-term follow up
and record any significant clinical bowel toxicity to validate the findings of the above research
that less-than-whole-uterus irradiation results in lower bowel doses.2

Article 3

The impact of imaging modality (CT vs MRI) and patient position (supine vs prone) on
tangential whole breast radiation therapy planning3


This small, dosimetric study evaluated differences between MRI and CT-derived PTVs in the
supine and prone positions for whole breast irradiation in breast cancer patients. Twenty-eight
patients were planned in both prone and supine positions, using both CT and MRI acquired
images for PTV delineation. The study found that there were no difference in various dose

metrics for the plans produced from either CT or MRI images. However, the odds of having a
sub-standard plan were much higher for prone positioning compared to supine positioning. Heart
volume was found to be higher in the supine position, but the mean heart dose was lower in the
supine position. Lung doses were better spared in the prone position, but contralateral breast dose
was significantly lower in the supine position. This latter finding contradicts previous research,
although placement of field borders differ between this study and previous studies.3

Future research:

Studies suggest that there is little clinical difference in lung doses between supine and prone
positions, whereas the heart is better spared in supine deep-inspiration-breath-hold techniques
than it is in the prone position.3,4 There is controversy over whether supine or prone position for
breast irradiation results in the lowest contralateral breast dose.3 A future dosimetric study would
aim to compare contralateral breast, lung, and heart doses in the prone and supine position, when
planned with differing field-placement techniques – such as field placement to markers placed at
CT-simulation, field placement to cover the CT-contoured breast tissue, and coverage of field-
derived (from the 50% isodose line) PTVs.

Article 4

Effect of reduction mammoplasty on acute radiation side effects and use of lumpectomy cavity


This single-institution review board-approved study examined the effects of reduction

mammoplasty (RM) during breast-conserving surgery on acute side-effects and lumpectomy
cavity boosts. Out of 650 treated patients, they identified 43 patients who had undergone a
reduction mammoplasty during breast-conserving surgery. There was no reported grade 3
toxicity difference between those patients that underwent reduction mammoplasty, and those that
didn’t. Fewer of the RM patients underwent a lumpectomy cavity boost, but there was concern
that RM may make the lumpectomy cavity hard to define.5

Future research:

The above study suggests alternative methods of defining the lumpectomy cavity (i.e. surgical
clips, or a bioabsorbable marker), or administering preoperative tumor boosts or intraoperative
radiation for those patients opting for RM, but potentially requiring a lumpectomy cavity boost.5
A prospective randomized trial would sort elective RM patients into three categories – traditional
delineation of lumpectomy cavity with postoperative tumor bed irradiation (following whole
breast irradiation), placement of a bioabsorbable marker at the time of the surgery and
postoperative tumor bed irradiation (following whole breast irradiation), and intraoperative or
preoperative tumor/tumor bed irradiation prior to whole breast irradiation. Long-term follow up
of patients would assess local recurrence failure rates for each arm, to compare with a control
group of non-RM patients receiving standard treatment.

Article 5

Real-time Online Matching in High Dose-per-Fraction Treatments: Do Radiation Therapists

Perform as Well as Physicians?6


This study was designed to determine if physicians were required to perform pre-treatment on-
set image matching prior to stereotactic body radiation therapy delivery, or if this task could be
delegated to the radiation therapists with no detriment to the delivery or to the patient. Within a
single institution, 16 radiation therapists (RTTs) and 5 physicians participated, with the RTTs
performing an initial online image match, noting the shifts, and then resetting the image. Blinded
to the RTT results, the physician would then perform the online image match and apply the shifts
for treatment. The resultant RTT and physician shifts were analyzed and compared. There was
no statistical significance found between the difference in shifts, leading the study to conclude
that, in their institution and without compromising patient safety, they could have the RTTs
perform the online match without the need for the physician to be present, and that the physician
would review the images offline when convenient.6

Future research:

The above study was conducted with SBRT treatments.6 At my clinic, we treat an increasing
amount of SRS treatments using ExacTrac, with the physician present for verification of the
image matching throughout the entire treatment. This is often a considerable amount of time out
of clinic or meetings for the physician, and so patients are scheduled according to physician
schedule, which is not always convenient. A future study could be undertaken at my institution,
using the same hypothesis and methods of the above study,6 but using the on-board CBCT
imaging and ExacTrac system with SRS treatments, with the aim of determining non-inferiority
of RTT image matches against physician image matches.


1. Foster B, Sindhu K, Hepel J et al. Three-Dimensional Bioabsorbable Tissue Marker

Placement is Associated with Decreased Tumor Bed Volume Among Patients Receiving
Radiation Therapy for Breast Cancer. Pract Radiat Oncol. 2019;9(2):e134-e141.
2. Kozak M, Koenig J, von Eyben R, Kidd E. Less Than Whole Uterus Irradiation for
Locally Advanced Cervical Cancer Maintains Locoregional Control and Decreases
Radiation Dose to Bowel. Pract Radiat Oncol. 2019;9(2):e164-e171.
3. Dundas K, Pogson E, Batumalai V et al. The impact of imaging modality (CT vs MRI)
and patient position (supine vs prone) on tangential whole breast radiation therapy
planning. Pract Radiat Oncol. 2018;8(3):e87-e97. doi:10.1016/j.prro.2017.07.007
4. Bartlett F, Colgan R, Donovan E et al. The UK HeartSpare Study (Stage IB):
Randomised comparison of a voluntary breath-hold technique and prone radiotherapy
after breast conserving surgery. Radiotherapy and Oncology. 2015;114(1):66-72.
5. Lin J, Bluebond-Langner R, Choi E et al. Effect of reduction mammoplasty on acute
radiation side effects and use of lumpectomy cavity boosts. Pract Radiat Oncol.
2017;7(5):e299-e308. doi:10.1016/j.prro.2017.01.005

6. 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?. Pract
Radiat Oncol. 2019;9(2):e236-e241. doi:10.1016/j.prro.2018.10.002