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Radiation Therapy VMAT Planning that Spares Ipsilateral SMG and

Level 1B Nodes For Oropharyngeal Head and Neck Cancers.

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.7 The 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 quality of life of patients.8 This benefit can be especially observed at night
when submandibular flow is strongly correlated to nighttime xerostomia.9 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.10 Side effects
can result in reduced nutritional intake and weight loss. This can significantly affect general
health and quality of life of the subjects involved.10 Typical head and neck cancer treatment
results in the submandibular gland (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 node involvement is rare. Lee et al2
showed for 102 patients observed from 2010 to 2016, only 4.3% had 1B nodal involvement.2 An
article by Francis Ho et al4 states that for level 1B nodes there is only a 2.7% chance of the nodes
being affected. Giuseppe Sanguineti et al6 stated that there is less than a 5% of the level 1B
nodes being impacted. Using volumetric modulated arc therapy (VMAT) to treat the patients
could also prove to be an advantage to maintain lower doses.3 Studies like Lee et al2
demonstrated that the percentage of 1B nodal involvement is rare, on top of that oropharynx
cancer rarely travels into the level 1B nodes. This means that SMG/1B nodes are considered low
risk for oropharynx cancer. The SMG is also included in the PTV because of its location to the
1B node but does not have any nodal drainage function. PTV volumes and treatments typically
include radiating the ipsilateral SMG and level 1B nodes. Irradiating the gland and node leads to
an increase in patients experiencing xerostomia and possibly a decrease in the patients’ quality of
life.1 Jackson et al1 demonstrated for the at-risk contralateral SMG and 1B nodes that it was
possible to spare them by maintaining a mean dose of ≤39 Gy. By adhering to these dose
constraints for the ipsilateral level 1B node and SMG there could be improved treatments
because it would decrease the risk of xerostomia and improve patients’ quality of life.1
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Therefore, this study will aim at testing the possibility of sparing irradiation to the ipsilateral
SMG and 1B nodes. The purpose of this study was to conclude if the SMG and level 1B nodes
could be spared while maintaining coverage to the PTV.

III. Methods and Materials

Patients diagnosed with oropharyngeal history of squamous cell carcinoma, base of

tongue (BOT), and tonsil head and neck cancer were considered for this study. Five patients
were collected from a single clinical location. These patients have already been treated using
radiation therapy for oropharyngeal head and neck cancer. The planning for this study will be
done retrospectively. The patients selected for this study have not had surgery to remove the
submandibular glands. Patients not eligible for this study included those that were considered
high risk, had metastatic disease to the lymph nodes, and/or gross tumor extending into the SMG.
The reason these patients are excluded is since we want to examine patients who have no nodal
or SMG involvement, but when treated the patients received radiation to these structures.
Computed Tomography scans were obtained during the simulation. For the simulation and
treatment, patients were positioned head-first, supine including the immobilization face mask in
the treatment area. The simulation was the same for all the selected patients, the treatment was
performed at a single institution, and the plans were all created by the same dosimetrist to
minimize variables in this study. The five scans utilized contrast and had a slice thickness of
3mm. Immobilization devices used are the 5-point thermoplastic mask, and s-frame.

Target volumes including gross tumor volume (GTV), clinical target volume (CTV), and
planning target volume (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 from the previous treatment will be recontoured by a Radiation Oncologist
for retrospective planning. The Radiation Oncologist found no nodal involvement or tumor
extending into the level 1B node or SMG. The contours for the target treatment volumes were
then reconstructed to account for the lack of disease involvement. 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 will be 5mm. The PRV expansion for the brain stem will be 3mm.
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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 66Gy. 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 6MV energy. The retrospective replans maintained the same optimization goals for
target coverage while aiming for improved OAR sparing, specifically the SMB and level 1B
nodes. Plans were optimized to the prescribed treatment volume. Normal tissue constraints for
the retrospective plans will be optimized with the goal of receiving the same or less dose than the
original plan. The normalization for all five plans will be the same. The normalization technique
that will be used is volume-based normalization. The normalization used is 95% of the PTV
volume receiving the prescription dose. The OAR structures for each patient will be re-planned
so that each structure receives equal or less dose than the original plan. The replans created will
be equally safe or safer to administer regarding normal structures within the head and neck. They
will also be 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.

Evaluation of the plans will be kept consistent from plan to plan. The planning target
coverage, dose to the SMG, dose to the level 1B node and dose to OAR structures will be the
primary focus of comparison. The coverage of the PTV will need to, at the least, meet 95%
volume covered by 100% dose. The main goal will be to match original prescribed coverage by
the Radiation Oncologist as well as match the PTV coverage from the original plan. While
maintaining coverage to the PTV sparing of the SMG is considered to have a mean dose of less
than 39 cGy. The dose to the ipsilateral SMG will be the next focus of comparison. Ensuring the
SMG is spared while achieving PTV coverage is the overall goal of the study. The dose the level
1B node will also be compared to the original plan. With the focus on sparing the level 1B node
as well. The level 1B node will be considered spared if it receives a mean dose of less than 29
cGy.5 The OAR structures that were compared via the two treatment plans for each patient
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. PTV coverage will be analyzed by the percentage of
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the target volume that is covered by the prescription dose or greater. The minimum coverage for
the plans will be the volume receiving 95% of the prescription dose (V95%). We will also be
comparing the volume receiving 100% of the prescription dose (V100%).

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 Organs At Risk (OARs)
that was equal to that of the original plan. The target coverage was assessed by measuring the
V95% and V100% with the new CTV. 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 will
be 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 70Gy, 63Gy, and 56Gy. 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 7640cGy to 7701cGy for an increase in .79%. The
mean dose for PTV 70 changed from 7212cGy to 7201cGy for a difference of .15%. PTV 63 had
a change in maximum dose from 7640cGy to 770cGy for a difference in .79%. The mean dose
for PTV 63 changed from 6724cGy to 6746cGY for a difference of .32%. PTV 56 had a change
in maximum dose from 6343cGy to 5860cGy for a change in 2.02%. The mean dose for PTV 56
changed from 6474 to 6051 for a difference of 3.15%. The retrospective plan had a maximum
hotspot change of 2% and mean dose change of 3%. Coverage of the target volume directlly
correlated to the original plan due to normalization. The dose differences in OAR structures are
below in figure 1.

Figure 1
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Patient 2 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70Gy, 63Gy, and 59.4Gy. 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 7817cGy to 7869cGy for a difference of .66%. The
mean dose for PTV 70 changed from 7323cGy to 7361cGy for a difference of .52%. PTV 63 had
a change in maximum dose from 7537cGy to 7741cGy for a difference in 2.29%. The mean dose
for PTV 63 changed from 6942cGy to 6901cGy for a difference of .59%. PTV 59.4 had a change
in maximum dose from 7817cGy to 7864cGy for a change in .66%. The mean dose for PTV 59.4
changed from 6454cGy to 6348cGy for a difference of 1.67%. The retrospective plan had a
maximum hotspot change of 2.3% and maximum mean dose change of 1.7%. Coverage of the
target volume directly correlated to the original plan due to normalization. The dose differences
in OAR structures are below in figure 2.

Figure 2
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Patient 3 had two PTV volumes being treated to three different doses. The doses to the
volumes included 63Gy and 54Gy. 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 7037cGy to 7102cGy for a difference of .92%. The mean dose
for PTV 63 changed from 6720cGy to 6757cGy for a difference of .55%. PTV 54 had a change
in maximum dose from 7043cGy to 7102cGy for a difference in .83%. The mean dose for PTV
54 changed from 5768cGy to 6209cGy for a difference of 7.10%. The retrospective plan had a
maximum hotspot change of 1% and maximum mean dose change of 7.1%. Coverage of the
target volume directly correlated to the original plan due to normalization. The dose differences
in OAR structures are below in figure 3.

Figure 3

Patient 4 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70Gy, 63Gy, and 56Gy. 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 7495cGy to 7626cGy for a difference of 1.72%.
The mean dose for PTV 70 changed from 7140cGy to 7140cGy for a difference of 1.72%. PTV
63 had a change in maximum dose from 7495cGy to 7626cGy for a difference of 1.72%. The
mean dose for PTV 63 changed from 6695cGy to 6662cGy for a difference of .26%. PTV 56 had
a change in maximum dose from 6448cGy to 6477cGy for a change in 1.96%. The mean dose
for PTV 56 changed from 5864cGy to 5967cGy for a difference of 1.73%. The retrospective plan
had a maximum hotspot change of 2% and maximum mean dose change of 1.8%. Coverage of
the target volume directly correlated to the original plan due to normalization. The dose
differences in OAR structures are below in figure 4.
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Figure 4

Patient 5 had three PTV volumes being treated to three different doses. The doses to the
volumes included 70Gy, 63Gy, and 56Gy. 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 7931cGy to 8013cGy for a difference of 1.02%.
The mean dose for PTV 70 changed from 7267cGy to 7323cGy for a difference of .76%. PTV 63
had a change in maximum dose from 7931cGy to 7960cGy for a difference of 1.15%. The mean
dose for PTV 63 changed from 6940cGy to 7021cGy for a difference of .36%. PTV 56 had a
change in maximum dose from 7613cGy to 7873cGy for a change in 1.58%. The mean dose for
PTV 56 changed from 6040cGy to 6137cGy for a difference of 3.30%. The retrospective plan
had a maximum hotspot change of 1.6% and maximum mean dose change of 3.3%. Coverage of
the target volume directly correlated to the original plan due to normalization. The dose
differences in OAR structures are below in figure 5.

Figure 5
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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% This means the retrospective plans
created were 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. Doses to the ipsilateral SMG exceeded
60Gy for three plans and only met the mean dose of 39Gy 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 if the ipsilateral SMG and level 1b node may need to be radiated in-order for a
functionable plan can be created. The main goal of this study was to help patients retain SMG
function. Studies suggest that a mean dose of less than 39 Gy will spare some salivary function
in the SMG.9 The retrospective planning was not able to accomplish mean doses that spare the
SMG and level 1b nodes. 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 amount of patients involved in this study would yield more favorable results. Sparing the
SMG and level 1b would help increase the patients quality of life.2 This study points towards the
point that a plan with adequate PTV coverage that spares the ipsilateral SMG/level 1b nodes is
unlikely to be achieved.

Conclusion
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The purpose of this study is not to change the way Radiation Oncologists draw CTV volumes
for oropharyngeal cancers. The volume that needs to be treated is up to the physician.

Since studies show the involvement of the SMG and level 1B are rare physicians could choose to
draw a volume to avoid these structures. This study aimed at demonstrating that if that were the
case a plan that is identical to a volume including the SMG/1B nodes can be created except for
the dose to those structures. The goal is to have a treatment that radiated the tumor volume the
same but spares the SMG level 1B node 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.3,7-9 This study does not supports the idea that a plan covering a PTV avoid
the SMG can receive the prescription dose and spare the SMG/1B nodes. The plan does support
the fact that a CTV drawn in this fashion still allows dose to the remaining OARs t 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.
Five plans are not a large enough sample size to show that plans like this can always be created.
More retrospective planning could be done to further this study. Studies tracking patient
outcomes after ipsilateral SMG and level 1b nodes should also be conducted in the future in-
order to prove that sparing these structures results in the same disease free statistics.
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References
1. 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.
2. 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
3. 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.
4. 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
 111

5. Chen J, Ou D, Hu C. Sparing level Ib lymph nodes by intensity-modulated radiotherapy

in the treatment of nasopharyngeal carcinoma. Int J Clin Oncol. 2013;19(6):998-1004.
http://dx.doi.org/10.1007/s10147-013-0650-6
6. 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
7. 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.
8. 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.
9. 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.
10. 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.