VMAT Planning to Reduce Ipsilateral Submandibular Gland and 1B Nodal Radiation for

Oropharyngeal Head and Neck Cancer

Luke VanLanen, BS; Nick Nguyen, BS, RT(T); Travis Kilmer, BS; Nishele Lenards PhD, CMD,
RT(R)(T), FAAMD; Karen Lang, MS, RT(T), CMD; Ashley Hunzeker, MS, CMD; Alyssa
Olson, MS, RT(T), CMD

Medical Dosimetry Program at the University of Wisconsin, La Crosse, WI

INTRODUCTION

The incidence of oropharynx cancer is on the rise with a predicted 53,000 new diagnoses
in 2019, according to the American Cancer Society.1 The submandibular gland (SMG) is a vital
gland in the human body that secretes saliva. It has been shown to produce 90% of unstimulated
saliva and, when spared, improve the patient’s quality of life.2 The improved quality of life can
be especially observed at night when submandibular flow is strongly correlated to nighttime
xerostomia.3 Patients with xerostomia have a hypofunction of salivary output resulting in sore
throat, altered taste, dental decay, changes in voice quality, and impaired chewing and
swallowing function.4 Side effects can result in reduced nutritional intake and weight loss. This
can significantly affect general health and quality of life.4

Typical head and neck cancer treatments result in the SMG and level 1B nodes receiving
high levels of radiation. Historically, level 1B nodes have been included in the treatment
volumes. This is contrary to many studies demonstrating that the percentage of 1B nodal
involvement is rare. Lee et al5 showed that for 102 patients observed from 2010 to 2016, only
4.3% had 1B nodal involvement. An article by Francis Ho et al6 states that for level 1B nodes
there is only a 2.7% chance of the nodes being affected. Sanguineti et al7 stated that there is less
than a 5% of the level 1B nodes being impacted. Studies like Lee et al5 demonstrated that the
percentage of 1B nodal involvement is rare, while oropharynx cancer rarely travels into the level
1B nodes. The seldom occurrence of 1B nodal involvement means that the SMG and 1B nodes
are considered low risk for oropharynx cancer. The SMG is also included in the planning target
volume (PTV) because of its location to the 1B nodes but does not have any nodal drainage
function. The treatment of PTV volumes typically includes irradiating the ipsilateral SMG and
level 1B nodes. Irradiating the gland and nodes leads to an increase in xerostomia and a potential
decrease in the quality of life for a patient.8 Jackson et al8 demonstrated the possibility of sparing
the at-risk contralateral SMG and 1B nodes by maintaining a mean dose of ≤ 39 Gy. In addition,
by adhering to the dose constraints for the ipsilateral level 1B nodes and SMG, the treatments
proved beneficial to the patients by decreasing the risk of xerostomia and improving quality of
life.8

Using volumetric modulated arc therapy (VMAT) to treat the patients could also prove to
be an advantage to maintain lower doses. Dai et al9 concluded that there was an improvement in
delivering lower doses to the mandible and oral cavity while also having improved target dose
homogeneity when compared to static-field intensity-modulated radiation therapy (IMRT). Other
advantages to using VMAT over static-field IMRT include having a shorter delivery time and a
smaller number of monitor units.9

The rise of oropharynx cancer diagnoses is increasing and the impact of irradiating the
SMG and level 1B nodes decreases the quality of life for many patients.1,2 With the 1B nodes
and SMG considered low risk for oropharynx cancer, the goal of this study focused on testing the
possibility of sparing irradiation to the ipsilateral SMG and 1B nodes while maintaining
coverage to the PTV utilizing VMAT. This was achieved by planning retrospective cases using a
reconstructed PTV created by a radiation oncologist.

Methods and Materials

Patient Selection & Setup

The selection criteria for this retrospective study included patients with a history of
oropharyngeal squamous cell carcinoma, base of tongue (BOT), or tonsil cancer and had
received prior radiation therapy to the oropharyngeal head and neck area. All the patients were
collected from a single clinical institution. A total of 5 patients were collected from a single
clinical location. One of the patients was treated bilateral, thus making a total of 6 sites. The
exclusion criteria for this study included patients not requiring surgical removal of SMGs,
considered high risk, had metastatic disease to the lymph nodes, and/or gross tumor extending
into the SMG.

Computed Tomography (CT) scans were obtained during the simulation. For the simulation,
patients were positioned head-first, supine including the immobilization face mask in the
treatment position. The immobilization devices used are the 5-point thermoplastic mask, s-frame.
The simulation was the same for all the selected patients. The five CT scans were performed
using contrast with a slice thickness of 3mm.

Target volumes including gross tumor volume (GTV), clinical target volume (CTV), and
PTV and were delineated by the radiation oncologist. Previously treated head and neck tumors
were re-planned with attempts to spare ipsilateral SMG and level 1B nodes. The PTV was
recontoured by a radiation oncologist for retrospective planning by placing a 3mm expansion on
the CTV. The PTV also had 5 mm subtracted from the skin contour. The radiation oncologist
found no nodal involvement or tumor extending into the level 1B nodes or SMG. The contours
for the target treatment volumes were then reconstructed to account for the lack of disease
involvement. The only change to the treatment volume in the retrospective plans was the absence
of the SMG and level 1b nodes. Normal structures contoured in all plans include; skin, mandible,
parotid gland, spinal cord, spinal cord Protective Ring Volume (PRV), brain, brain stem, brain
stem PRV, optic nerve, optic chiasm, orbit, and lens. The PRV expansion for the spinal cord was
be 5mm. The PRV expansion for the brain stem was 3mm.

Patients in this study were treated with doses ranging from 66-70 Gy. Four of the patients
were treated to 70 Gy and only one patient was treated to 66 Gy. The reason this patient was
treated to 66 Gy was because the pathology report indicated the patients' stage as T1 N0 M0.
With no metastatic disease, no node involvement, and the tumor can only be detected from a
biopsy at the time of consultation are the reasons that warrant a lower prescription dose. All
treatment regimens were given prescriptions that matched the standard of care. The prescriptions
matched the treatment plan that the patient was originally treated with. The treatment planning
systems (TPS) used for the planning of all five patients was Monaco (Elekta). Treatment plans
were generated using a VMAT technique consisting of 2-3 arcs and 360 degrees of rotation. The
plans were re-created all using 6 MV energy. The retrospective re-plans aimed to maintain the
same optimization goals for target coverage while improved organs at risk (OAR) sparing were
optimized with the goal of receiving the same or less dose than the original plan. Each plan was
normalized using a volume-based normalization technique. The normalization used is 95% of the
PTV volume receiving the prescription dose. The OAR structures for each patient re-planned so
that each structure receives equal or less dose than the original plan. The re-plans created were
equally safe or safer to administer regarding normal structures within the head and neck. They
were also equally effective at treating the tumor mass since the only difference in the plans is the
avoidance of the ipsilateral SMG/1B nodes, which were found to be disease free.

The primary focus of comparison is planning target coverage, dose to the SMG, dose to
the level 1B nodes and dose to OAR structures. Evaluations of individual plans were kept
consistent for each plan. The PTV coverage was analyzed by the percentage of the target volume
that is covered by the prescription dose or greater. The minimum coverage for the plans was the
volume receiving 95% of the prescription dose (V95%). We also compared the volume receiving
100% of the prescription dose (V100%). Each plan needed to, at the least, meet 95% of the volume
covered by 100% of the prescription dose. The main goal was to match original prescribed
coverage by the radiation oncologist as well as match the PTV coverage from the original plan.
The dose to the ipsilateral SMG was the next focus of comparison. While maintaining coverage
to the PTV, sparing of the SMG is considered successful if it has a mean dose of less than 39 Gy.
Ensuring the SMG is spared while achieving PTV coverage is the overall goal of the study along
with sparing the level 1B nodes as well. Next, the dose at the level 1B nodes was compared to
the original plan. The level 1B nodes was considered successfully spared if it receives a mean
dose of less than 29 Gy.10 Finally, the OAR structures were compared via the two treatment
plans for each patient that include the following: mandible, parotid gland, spinal cord, spinal
cord PRV, brain, brain stem, brain stem PRV, optic nerve, optic chiasm, orbit, and lens.
Maximum mean doses are to be recorded for the contoured structures at risk.

Results

The results from the new plans created in this study demonstrated that acceptable PTV
coverage was achievable. The plans were also able to deliver dose to the OAR that was equal to
that of the original plan. The target coverage was assessed by measuring the V 95% and V100% with
the new target volumes. All plans met the PTV coverage goal when assessing the percentage of
PTV volume covered by the prescription dose. The results from the five plans were evaluated
individual to illustrate the identical nature of both plans.

Patient 1 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70 Gy, 63 Gy, and 56 Gy. The normalization for the PTV’s was kept the same
such that 95% of the volumes were covered by the prescription dose. In the retrospective plan
PTV 70 had a change in maximum dose from 76.40 Gy to 77.01Gy for an increase in 0.79%. The
mean dose for PTV 70 changed from 72.12 Gy to 72.01 Gy for a difference of -0.15%. For PTV
63 there was a change in maximum dose from 76.40 Gy to 7.70 Gy for a difference in 0.79%.
The mean dose for PTV 63 changed from 67.24 Gy to 67.46 Gy for a difference of 0.32%. For
PTV 56 there was a change in maximum dose from 63.43 Gy to 58.60 Gy for a change in 2.02%.
The mean dose for PTV 56 changed from 64.74 Gy to 60.51 Gy for a difference of 3.16%. The
retrospective plan had a maximum hotspot change of 2.02% and mean dose change of 3.16%.
Coverage of the target volume directly correlated to the original plan due to normalization. The
dose differences in OAR structures are below in Table 1.

Patient 2 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70 Gy, 63 Gy, and 59.4 Gy. The normalization for the PTV’s was kept the
same such that 95% of the volumes were covered by the prescription dose. In the retrospective
plan PTV 70 had a change in maximum dose from 78.17 Gy to 78.69 Gy for a difference of
0.66%. The mean dose for PTV 70 changed from 73.23 Gy to 73.61 Gy for a difference of
0.52%. The PTV 63 had a change in maximum dose from 75.37 Gy to 77.41 Gy for a difference
in 2.29%. The mean dose for PTV 63 changed from 69.42 Gy to 69.01 Gy for a difference of -
0.59%. For PTV 59.4, it had a change in maximum dose from 78.17 Gy to 78.64 Gy for a change
in 0.66%. The mean dose for PTV 59.4 changed from 64.54 Gy to 63.48 Gy for a difference of -
1.67%. The retrospective plan had a maximum hotspot change of 2.30% and maximum mean
dose change of -1.67%. Coverage of the target volume directly correlated to the original plan due
to normalization. The dose differences in OAR structures are below in Table 2.

Patient 3 had two PTV volumes being treated to three different doses. The doses to the
volumes included 63 Gy and 54 Gy. The normalization for the PTV’s was kept the same such
that 95% of the volumes were covered by the prescription dose. In the retrospective plan PTV 63
had a change in maximum dose from 70.37 Gy to 71.02 Gy for a difference of 0.92%. The mean
dose for PTV 63 changed from 67.20 Gy to 67.57 Gy for a difference of 0.55%. For PTV 54, it
had a change in maximum dose from 70.43 Gy to 71.02 Gy for a difference in 0.83%. The mean
dose for PTV 54 changed from 57.68 Gy to 62.09 Gy for a difference of 7.10%. The
retrospective plan had a maximum hotspot change of 0.92% and maximum mean dose change of
7.10%. Coverage of the target volume directly correlated to the original plan due to
normalization. The dose differences in OAR structures are below in Table 3.

Patient 4 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70 Gy, 63 Gy, and 56 Gy. The normalization for the PTV’s was kept the same
such that 95% of the volumes were covered by the prescription dose. In the retrospective plan
PTV 70 had a change in maximum dose from 74.95 Gy to 76.26 Gy for a difference of 1.72%.
The mean dose for PTV 70 changed from 71.40 Gy to 71.40 Gy for a difference of 1.72%. For
PTV 63, it had a change in maximum dose from 74.95 Gy to 76.26 Gy for a difference of 1.72%.
The mean dose for PTV 63 changed from 66.95 Gy to 66.62 Gy for a difference of 0.26%. For
PTV 56, it had a change in maximum dose from 64.48 Gy to 64.77 Gy for a change in 1.96%.
The mean dose for PTV 56 changed from 58.64 Gy to 59.67 Gy for a difference of 1.73%. The
retrospective plan had a maximum hotspot change of 1.96% and maximum mean dose change of
1.73%. Coverage of the target volume directly correlated to the original plan due to
normalization. The dose differences in OAR structures are below in Table 4.

Patient 5 had three PTV volumes being treated to three different dose levels. The doses to
the volumes included 70 Gy, 63 Gy, and 56 Gy. The normalization for the PTV’s was kept the
same such that 95% of the volumes were covered by the prescription dose. In the retrospective
plan PTV 70 had a change in maximum dose from 79.31 Gy to 80.13 Gy for a difference of
1.02%. The mean dose for PTV 70 changed from 72.67 Gy to 73.23 Gy for a difference of
0.76%. For PTV 63, it had a change in maximum dose from 79.31 Gy to 79.60 Gy for a
difference of 1.15%. The mean dose for PTV 63 changed from 69.40 Gy to 70.21 Gy for a
difference of 0.36%. For PTV 56, it had a change in maximum dose from 76.13 Gy to 78.73 Gy
for a change in 1.58%. The mean dose for PTV 56 changed from 60.40 Gy to 61.37 Gy for a
difference of 3.30%. The retrospective plan had a maximum hotspot change of 3.30% and
maximum mean dose change of 1.58%. Coverage of the target volume directly correlated to the
original plan due to normalization. The dose differences in OAR structures are below in Table 5.

Discussion

The results of this study show that a CTV drawn to avoid the ipsilateral SMG and level
1B nodes can replicate a plan that includes those structures in the treatment volume. The results
demonstrated adequate coverage to a PTV drawn to spare the SMG/level 1B nodes can be
achieved. Although comparing PTV coverage from the original plan to the new plan does not say
much about tumor coverage since they are not the same volume. We were still able to
demonstrate that PTV coverage was either equal or better in the new plan. Utilizing mean dose to
measure the dose to the target volume allows for a great comparison. In this study only one
outlier occurred. In patient 3 the mean dose for PTV 54 changed by 7%. Other than this one
volume the PTV mean doses never varied by greater than 5% demonstrating that the
retrospective plans were created very similar to the original plan. Although PTV coverage was
met, the mean doses to the ipsilateral SMG and level 1B nodes were not met. The main goal of
this study was to help patients retain SMG function. Researchers suggest that a mean dose of less
than 39 Gy spares some salivary function in the SMG.3 Doses to the ipsilateral SMG exceeded
60 Gy for three plans and only met the mean dose of 39 Gy for one plan. This means that only
20% of the plans were able to spare the SMG, and 60% of the plans exceeded 60 Gy. This
suggests that in many instances the ipsilateral SMG and level 1B nodes can not be spared for a
functionable plan to be created. Although, sparing the SMG and level 1B nodes may be an option
a radiation oncologist would explore it may not be possible to achieve that plan. An aspect that
may be noted is that this study only investigated five patients. It may be possible that expanding
the number of patients involved in this study would yield more favorable results. Sparing the
SMG and level 1B would help increase the patient's quality of life.5 This study demonstrates that
a plan with adequate PTV coverage that spares the ipsilateral SMG/level 1B nodes is unlikely to
be achieved.

Conclusion

The purpose of this study was to conclude if the SMG and level 1B nodes could be
spared while maintaining coverage to the PTV for patients with oropharyngeal cancer. The goal
is to have a treatment that irradiated the tumor volume the same but spares the SMG and level 1B
nodal function. When considering mean dose to the ipsilateral SMG and level 1B nodes, the
findings of this study do not support the idea that an attempt to spare could be made. Multiple
studies have shown the potential benefit of sparing the salivary function of a patient. 9, 1-3 This
study does not support the idea that a plan can maintain coverage to the PTV and spare the
SMG/1B nodes for patients with oropharyngeal cancer. The plan does support the fact that a
CTV drawn in this fashion still allows dose to the remaining OARs to meet planning constraints
and varied very slightly from the original plans. Finally, we want to conclude this study by
stating that this study should be expanded to more retrospective planning. One of the limitations
of this study was the number of patients evaluated for re-planning. To further research in this
area of treatment our study should be replicated but with a larger number of patients. A larger
sample size would give a better idea of the types of patients this type of planning technique could
benefit.
 References

1. Key Statistics for Oral Cavity and Oropharyngeal Cancers. American Cancer Society.
https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-
statistics.html. Accessed June 24, 2019.
2. Gensheimer M, Liao J, Laramore G, Parvathaneni U. Safety of Submandibular Gland-
Sparing Intensity Modulated Radiation Therapy for Head-and-Neck Cancer. Int J Radiat
Oncol Biol Phys. 2013;87(2). http://dx.doi.org/10.1016/j.ijrobp.2013.06.153
3. Terhaard C, Dijkema T, Braam P, Raaijmakers C, Roesink J. Importance of Sparing
Submandibular Gland Function to Improve Patient-reported Xerostomia. Int J Radiat
Oncol Biol Phys. 2010;78(3). http://dx.doi.org/10.1016/j.ijrobp.2010.07.218
4. Pinna R, Campus G, Cumbo E, Mura I, Milia E. Xerostomia induced by radiotherapy: an
overview of the physiopathology, clinical evidence, and management of the oral damage.
Ther Clin Risk Manag. 2015:171. http://dx.doi.org/10.2147/tcrm.s70652
5. Lee NC, Kelly JR, Park HS, Yarbrough WG, Burtness BA, Husain, ZA. (2017). The risk
of level IB nodal involvement in oropharynx cancer: Guidance for submandibular gland
sparing irradiation. Pract Radiat Oncol. 2017;7(5): e317-e321.
http://dx.doi.org/10.1016/j.prro.2017.02.004
6. Ho FCH, Tham IWK, Earnest A, Lee KM, Lu JJ. Patterns of regional lymph node
metastasis of nasopharyngeal carcinoma: A meta-analysis of clinical evidence. BMC
Cancer. 2012;12(1). http://dx.doi.org/10.1186/1471-2407-12-98
7. Sanguineti G, Califano J, Zhou J, Stafford E, Koch W, Tufano R, Gourin C, Sormani M,
Marur S, Forastiere A. Defining the Risk of Involvement for each Neck Nodal Level in
Patients with Early T-stage/Node-positive Oropharyngeal Carcinoma. Int J Radiat Oncol
Biol Phys. 2008;72(1). http://dx.doi.org/10.1016/j.ijrobp.2008.06.506
8. Jackson WC, Hawkins PG, Arnould GS, Yao J, Mayo C, Mierzwa M. Submandibular
gland sparing when irradiating neck level IB in the treatment of oral squamous cell
carcinoma. Med Dosim. 2019;44(2):144-149.
http://dx.doi.org/10.1016/j.meddos.2018.04.003
9. Dai X, Zhao Y, Liang Z, Dassarath M, Wang L, Jin L, Chen L, Dong J, Price RA, Ma
CM. Volumetric-modulated arc therapy for oropharyngeal carcinoma: A dosimetric and
 delivery efficiency comparison with static-field IMRT. Physica Medica. 2015;31(1):54-
59. http://dx.doi.org/10.1016/j.ejmp.2014.09.003
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http://dx.doi.org/10.1007/s10147-013-0650-6
 Tables

Table 1. Reported percent differences between the original plan and the retrospective plan for
patient 1. The table compares the revised plan to the original plan.
Table 2. Reported percent differences between the original plan and the revised plans for patient
2. The table compares the revised plan to the original plan.
Table 3. Reported percent differences between the original plan and the retrospective plan for
patient 3. The table compares the revised plan to the original plan.
Table 4. Reported percent differences between the original plan and the retrospective plan for
patient 4. The table compares the revised plan to the original plan.
Table 5. Reported percent differences between the original plan and the retrospective plan for
patient 5. The table compares the revised plan to the original plan.