Research Proposal: Quantitative

Title: Delineating the lumbosacral plexus as an organ at risk to measure the unwanted dose this
structure receives in treating pelvic cancers with volumetric modulated arc therapy (VMAT).
Literature Review Summary
The occurrence of radiation-induced lumbosacral plexopathy (RILSP) is widely
underreported even though the symptoms patients experience are often debilitating and severely
affect the quality of life. Radiation-induced lumbosacral plexopathy has a wide range of onset,
from 1-3 months to years or more after treatment.1 A major consideration of the underreporting
is that radiation oncologists are not involved in long-term follow-up care, thereby reducing the
amount of diagnoses of RILSP.1 Typically, symptoms are reported to the patient’s primary care
physician and can still be difficult to diagnose due to comorbidities and difficulty with
differential diagnoses. Although reported cases are rare, published data suggest that the reported
frequency of RILSP in gynecological malignancies range from 1.3% to 6.67%, with reporting
clinical symptoms of varying degrees of bilateral limb weakness, numbness, paralysis, and
possibly urinary and fecal incontinence.1-3 The primary goal of pelvic irradiation treatments is to
eradicate the tumor volume while sparing normal surrounding tissues such as the LSP and
minimizing side effects and patient complications like RILSP. With cases of RILSP still being
reported, it is worth investigating the potential cause to reduce the likelihood of occurrence.
Today, pelvic cases are widely treated using intensity modulated radiation therapy
(IMRT). While the use of IMRT has advantages, a significant disadvantage is “dose-dumping” in
the lumbosacral region. Doses in this region reach high levels that may cause RILSP due to the
absence of the delineation and consideration of lumbosacral plexus (LSP) as an organ at risk
(OAR). It is understood that the pelvic cases utilizing IMRT technique, often involve para-aortic
nodes and concomitant chemotherapy, making the nerves radiosensitive in pelvic sites of rectal,
anal, lymphoma, and gynecological malignancies. Tunio et al3 noted that there was an 8%
increase in the incidence of RILSP in their study compared to other published data with an
average incidence of 4%. Tunio et al.3 also suggested that concomitant chemotherapy may be a
factor in the incidence of RILSP due to increased radio-sensitivity of peripheral nerves. This
increased sensitivity can lead to RILSP in doses as low as 50-60 Gy, in cases where pelvic
malignancies are treated with concurrent chemotherapy and radiation therapy.3 The incidence of
RILSP can potentially be decreased by delineating the LSP as an OAR.
 Yi et al5 published a standardized method of delineating the LSP and established
preliminary dosimetric parameters for future use by researchers to measure the dose-risk
relationship of RILSP. Yi et al5 approached their study with respect to the Radiation Therapy
Oncology Group (RTOG), citing the current mandate of OAR contouring instructions for all
clinical trials in IMRT treatment planning. The accuracy of delineation of all OAR is essential to
avoiding dose to normal surrounding tissues while successfully meeting dose objectives to the
target volume. Since the LSP is not routinely delineated for pelvic IMRT planning, nor required
to be delineated on current Phase II protocols where IMRT rectal or anal cancers are evaluated, it
may lead to “dose-dumping” in the LSP region because it is not defined as an OAR.5 While Yi et
al5 established a standardized method of delineating the LSP another group of researchers
suggested an alternate way of contouring. Min et al2 concluded that a generalized lumbosacral
plexus region (LSPR) was more appropriate in delineating the LSP because this contouring
strategy would take into account the area where the LSP is not visible on imaging and suggested
that the radiation oncologist practice “nerve-sparing” in radiotherapy.2,6 The increased volume of
the LSPR led to further studies on “dose dumping” to this region.
Published research from Tunio et al3 sought to correlate dose distributions in LSP and
RILSP in cervical cancer patients using IMRT and intracavitary high-dose rate (HDR)
brachytherapy using a sample size of 50 patients treated with radiation during 2007-2012. At a
60 month follow up, 4 patients (8%) had developed grade 2/3 RILSP. Using the Yi et al5 LSP
contour guidelines, Tunio et al3 established quantifiable data to correlate the dose to LSP that
could cause RILSP but cited limitations of a small sample size and rather short period of follow-
up. The dosimetric mean values calculated by Tunio et al3 suggested a correlation between dose
distribution within the LSP and RILSP. A 12% increase in RILSP was found when the mean
volume percentage of the LSP received, respectively 40, 50, and 55 Gy (V40, V50 and V55).3 The
problem is that the LSP is not a standard delineated OAR for pelvic-paraaortic irradiation
resulting in no dose tracking during volumetric modulated arc therapy (VMAT) treatments and a
potentially higher V40 and V50. Limitations from previous research studies suggested that further
quantitative analysis must be conducted with a larger cohort sample to establish a correlation
with absence of delineating the LSP as an OAR and dose-dumping into the LSP region.2,3 The
purpose of this study is to delineate the LSP as an OAR to compare doses to volumetric
constraints in VMAT planned pelvic cases while maintaining acceptable target coverage.
Problem Statement
The problem is that the LSP is not a standard delineated OAR for pelvic-paraaortic irradiation
resulting in no dose tracking during VMAT treatments and potentially higher V40 and V50.
Purpose Statement
The purpose of this study is to delineate the LSP as an OAR to compare doses to volumetric
constraints in VMAT planned pelvic cases while maintaining acceptable target coverage.
Hypothesis
The research hypothesis (H1A) is that the researchers will be able to lower the V40 to the LSP and
maintain acceptable target coverage. The null hypothesis (H10) is that the researchers will not be
able to lower V40 to the LSP and maintain acceptable target coverage. The research hypothesis
(H2A) is that the researchers will be able to lower the V50 to the LSP and maintain acceptable
target coverage. The null hypothesis (H20) is that the researchers will not be able to lower V50 to
the LSP and maintain acceptable target coverage.
Methods and Materials
Patient Selection
Patients who have been treated for lower GI (rectal and anal) or Pelvic (gynecological and
lymphoma) cancers with paraaortic nodal involvement using VMAT. Twenty to thirty patients
from two radiation oncology departments will be selected for this retrospective study.
Planning Procedures
Two radiation oncology residents will delineate the LSP in patients who were treated for a lower
GI or pelvic malignancy with VMAT. The treatment planning in these pelvic cases includes
paraaortic nodal involvement. The mean values of V40 and V50 will be measured and recorded.
Evaluated Variables
A retrospective study will be completed for each patient using the original plan. From the
original plan, a new VMAT treatment plan will be created with the LSP delineated as an OAR.
The mean values of V40 and V50 to the LSP will be measured and recorded to prove that a
delineated LSP will result in lower dose.
 References
1. Vinciguerra C, Nardone V, Sicurelli F, Guida C, Cappabianca S. Lumbosacral plexopathy in
pelvic radiotherapy: An association not to be neglected; A systematic review, Arch Neurosci.
2019;6(4):1-6. http://dx.doi.org/10.5812/ans.86686
2. Min M, Roos D, Keating E, et al. External validation of the lumbosacral plexus-contouring
protocol developed by Yi et al. (IJROBP 2012; 84: 376-82) for pelvic malignancies. J Med
Imaging  Radiat Oncol. 2014;58:117-124. http://dx.doi.org/10.111/1754-9485.12106
3. Tunio M, Al Asiri M, Bayoumi Y, et al. Lumbosacral plexus delineation, dose distribution,
and its correlation with radiation-induced lumbosacral plexopathy in cervical cancer
patients. Onco Targets  Ther.  2015;8:21-27. http://dx.doi.org/10.2147/OTT.S71086
4. Delanian S, Lefaix J, Pradat P. Radiation-induced neuropathy in cancer survivors. Radiat
Oncol. 2012;105(3):273-282. http://dx.doi.org/10.1016/j.radonc.2012.10.012
5. Yi S, Mak W, Yang C, et al. Development of a standardized method for contouring the
lumbosacral plexus: a preliminary dosimetric analysis of this organ at risk among 15 patients
treated with intensity-modulated radiotherapy for lower gastrointestinal cancers and the
incidence of radiation-induced lumbosacral plexopathy. Int J Radiat Oncol Biol Phys.
2012;84(2):376-382. http://dx.doi.org/10.1016/j.ijrobp.2011.11.074
6. Bourhafour I, Benoulaid M, El Kacemi H, El Majjaoui S, Kebdani T, Benjaafar N.
Lumbosacral plexopathy: A rare long-term complication of concomitant chemo-radiation for
cervical cancer. Gynecol Oncol Res Pract. 2015;2(12):1-4. http://dx.doi.org/10.1186/s40661-
015-0019-9