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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 65-69

Dosimetric evaluation of dorsal vagal complex and vestibular apparatus in head-and-neck cancer patients treated with intensity-modulated radiotherapy


Advanced Centre for Radiation Oncology, Nanavati Superspeciality Hospital, Mumbai, Maharashtra, India

Date of Submission15-Feb-2021
Date of Acceptance20-Feb-2021
Date of Web Publication04-May-2021

Correspondence Address:
Dr. Tauseef Ali
Advanced Centre for Radiation Oncology, Nanavati Superspeciality Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_6_21

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  Abstract 


Purpose: The purpose of this study was to dosimetrically evaluate the dose received by dorsal vagal complex (DVC) and vestibular apparatus in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). Materials and Methods: Twenty histopathologically confirmed head-and-neck cancer patients, preferably oropharynx and nasopharynx that were treated with IMRT from a period of 2018–2020, were retrospectively analyzed in this study. DVC and vestibular apparatus were contoured, and the doses received by them were noted. Results: The average minimum dose to the entire DVC and vestibular apparatus was 25.134 Gy (range, 8.77–37.49 Gy) and 12.812 Gy (range, 1.07–28.57 Gy); the average maximum point dose to the DVC and vestibular apparatus was 35.896 Gy (range, 24.29–45.53 Gy) and 33.266 Gy (range, 3.19–60.72 Gy); and the average mean dose to the entire DVC and vestibular apparatus volume was 30.151 Gy (range, 16.48–40.83 Gy) and 21.484 Gy (range, 2.99–39.42 Gy), respectively; the average volume of DVC and vestibular apparatus was 0.52 cm3 (range, 0.3–0.8 cm3) and 0.36 (range, 0.2–0.6 cm3), respectively. Conclusions: Considering the DVC and vestibular apparatus as an organ for conformal avoidance, there can be a possibility in the reduction of nausea and vomiting while treating patients of head-and-neck cancer with radiation.

Keywords: Dorsal vagal complex, emetic centers, radiation-induced nausea and vomiting


How to cite this article:
Ali T, Singh A, Parab A. Dosimetric evaluation of dorsal vagal complex and vestibular apparatus in head-and-neck cancer patients treated with intensity-modulated radiotherapy. J Radiat Cancer Res 2021;12:65-9

How to cite this URL:
Ali T, Singh A, Parab A. Dosimetric evaluation of dorsal vagal complex and vestibular apparatus in head-and-neck cancer patients treated with intensity-modulated radiotherapy. J Radiat Cancer Res [serial online] 2021 [cited 2021 Sep 22];12:65-9. Available from: https://www.journalrcr.org/text.asp?2021/12/2/65/315465




  Introduction Top


Nausea and vomiting are one of those side effects, that deteriorate the patient physically as well as mentally, especially a patient suffering from head-and-neck cancer on treatment with radiation therapy. A multicenter Italian observational trial had demonstrated that radiation-induced emesis occurred in about 40% of head-and-neck cancer patients treated with conventional radiation techniques.[1] Meanwhile, there are many reasons which include thick salivary secretions, altered taste sensations, and so on, causing nausea and vomiting in a patient of head-and-neck cancer undergoing radiation therapy; the one aspect less considered is radiation dose to the emetic centers present in the brain.

Intensity-modulated radiotherapy (IMRT), using multiple beams with fluence of photons modified by multi-leaf collimators, has changed the paradigm of radiotherapy by reducing the doses to the organ at risk, providing better conformality and optimal dose distribution to the target volumes, but at the same time has caused an increase of low-dose deposition to nontarget tissues. Fan. in their study of head-and-neck cancer patients treated with IMRT have observed a higher incidence of nausea and vomiting irrespective of cisplatin chemotherapy use.[2]

Area postrema (AP), nucleus of solitary tract, and dorsal vagal nucleus together forming the dorsal vagal complex (DVC) constitute the emetic center in the brain stem.[3] AP present in the medulla oblongata located in the dorsal surface of the fourth ventricle detects emetogenic substances traveling via cerebrospinal fluid and blood; these signals are then conveyed to the dorsal vagal nucleus, where the vagal afferent nerve fibers terminate. Monroe in his study was able to demonstrate a correlation between the dose received by DVC and its relation to vomiting.[4]

Lee observed a correlation between the dose to vestibular apparatus for patients with nasopharyngeal carcinoma.[5] Vestibular apparatus with the cochlea forming the inner ear is known to provide spatial orientation and balance. Any pathology of the vestibular apparatus would lead to dizziness eventually causing nausea and vomiting. Young in his study showed that patients receiving radiation for nasopharyngeal carcinoma had vertigo as a late complication with a mean interval of 10 years.[6]

In our study, we have done a dosimetric evaluation and tried to find out the dose received by the DVC and vestibular apparatus.


  Materials and methods Top


Patients

Twenty histopathologically confirmed patients suffering from head-and-neck cancer, preferably oropharynx and nasopharynx that were treated from a period of 2018–2020, were retrospectively analyzed in this study [patient characteristics are summarized in [Table 1]]. All patients were of squamous cell carcinoma histology except one which was a neuroendocrine tumor and all were treated with IMRT. Almost all patients received chemotherapy, mainly with cisplatin concurrently. Patients were immobilized using a thermoplastic mask over the head and shoulders. A planning computed tomography (CT) scan of 3 mm slice thickness was obtained from vertex to upper mediastinum. All patients were treated with conventional fractionation with cumulative doses ranging from 55 to 70 Gray (Gy) based on the preference of the radiation oncologist and clinical condition of the patient. Radiation was delivered to patients on Halcyon 2.0 linear accelerator from Varian Medical Systems, USA, using 6 MV photons.
Table 1: Patient characteristics

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Target volumes and treatment planning

The gross target volume (GTV) comprised the primary tumor and nodes that were clinically or radiographically visible. The clinical target volume (CTV) consisted of the GTV along with areas of microscopic spread and the regional nodal areas harboring a risk for metastasis. The planning target volume (PTV) comprised the CTV with a 5 mm uniform expansion to compensate for the treatment setup errors and internal organ motion. Positron emission tomography or magnetic resonance imaging (MRI) images were co-registered if available with the planning CT to assist with target delineation.

Organs at risk were contoured that included the parotid gland, spinal cord, brain stem, optic nerves, lens, and posterior globes.

Then, plan optimization was done using an inverse planning module which used anisotropic analytical algorithm (AAA), with a calculation grid of 0.25 cm.

Target volume coverage goals included the delivery of the prescribed dose to at least 95% volume of the PTV. All patients had received elective treatment to the lower neck except for one patient with neuroendocrine tumor as its histology. DVC and vestibular body were not assigned as a critical structure and were not delineated for avoidance.

Dorsal vagal complex and vestibular apparatus contouring

DVC was contoured as per the anatomical contouring guidelines by O'Steen and Amdur.[7] It was contoured in the mid-medulla that is halfway between the slice that contained the most inferior edge of the pons (the last slice where cerebellar peduncles were visible) and the most superior slice that contained the spinal cord. The anterior boundary was the center of the medulla, the posterior boundary was the posterior surface of the medulla, and the lateral boundary constituted the lateral surface of the medulla. Cranial and caudal borders were 1 slice above and 1 slice below the mid-medulla. [Figure 1] shows the location of DVC in the axial image.
Figure 1: Location of dorsal vagal complex in axial image

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The right and left vestibular apparatus were also contoured. Vestibular apparatus are ovoid bony structures that have to be visualized in the bone window of CT scan and are located just above and posterolateral to the internal acoustic meatus. [Figure 2] shows the location of the vestibular apparatus in the axial image.
Figure 2: Location of vestibular apparatus in axial image

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For all patients, brain stem, DVC and vestibules were contoured by the same radiation oncologist to eliminate interobserver variability.

Statistical analysis

Ranges of dose–volume statistics for every patient's DVC and vestibular apparatus were calculated. The maximum DVC and vestibular apparatus dose (Dmax), mean DVC and vestibular apparatus dose, and minimum DVC and vestibular apparatus dose were analyzed.


  Results Top


The average minimum dose to the entire DVC and vestibular apparatus volume was 25.134 Gy (range, 8.77–37.49 Gy) and 12.812 Gy (range, 1.07–28.57 Gy), respectively; the average maximum point dose to the DVC and vestibular apparatus volume was 35.896 Gy (range, 24.29–45.53 Gy) and 33.266 Gy (range, 3.19–60.72 Gy), respectively; the average mean dose to the entire DVC and vestibular apparatus volume was 30.151 Gy (range, 16.48–40.83 Gy) and 21.484 Gy (range, 2.99–39.42 Gy), respectively; the average volume of DVC and vestibular apparatus was 0.52 cm3 (range, 0.3–0.8 cm3) and 0.36 (range, 0.2–0.6 cm3), respectively.

[Table 2] shows the disease site; total dose to target volumes; maximum, minimum, and mean dose to DVC and vestibular apparatus; and volume of DVC and vestibular apparatus of all 20 patients.
Table 2: Dorsal vagal complex and vestibular apparatus dosimetric characteristics

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  Discussion Top


DVC even though situated in the brain stem has a lower constraint value in comparison to the conventional constraints that is 54 Gy for the entire brain stem. Monroe et al. in their recent study had analyzed 70 head-and-neck cancer patients that did not receive concurrent cisplatin-based chemotherapy. They had included patients receiving cetuximab, given the lower rates of nausea associated with cetuximab.[8] They observed on univariate and multivariate analysis that T stage and DVC dose were significant predictors of nausea. They concluded that the DVC doses >30 Gy were associated with a higher rate of nausea. Out of 20 patients, we were able to achieve this dose constraint in 11 patients. However, none of our patients experienced nausea and vomiting as many of our patients were provided prophylactic antiemetics while undergoing radiation therapy, and some had received antiemetics as a part of chemotherapy.

Wang et al. in their retrospective analysis of oropharyngeal patients had observed that a median DVC dose of 40.4 Gy and dose to AP of 38.7 Gy were associated with the complaints of nausea. They also had replanned their patients and were able to reduce the dose to DVC and AP without compromising their target volume coverage.[9] Hence, by considering the DVC as an organ for conformal avoidance, there can be a reduction in the possibility for one of that toxicity that is dreaded in head-and-neck radiation.

In a prospective study done by Lee et al., they had enrolled around 49 patients of nasopharyngeal carcinoma, which were either early stage that could just be treated with external beam radiotherapy alone or those cases where chemotherapy was contraindicated due to the patient's noteworthy medical comorbidities. They had contoured DVC and vestibular bodies as organs at risk but had given no weightage to these structures during plan optimization. In the univariate analysis, they found that the volume receiving 40 Gy to both vestibules combined being more than 80% was a significant predictor of radiation-induced acute nausea. They could not establish a significant relation between DVC and radiation-induced acute nausea.[5] In our study, we observed that the average mean dose received by the vestibular apparatus was 21.484 Gy.

Meanwhile, few studies were not able to show a significant dose relationship between DVC and nausea. Ciura et al. retrospectively analyzed 100 head-and-neck cancer patients but could not show a statistically significant relation between the dose to DVC and episodes of nausea. They did note that nausea and vomiting developed around the 2nd week of treatment with radiotherapy, creating a possibility that a dose of 15–25 Gy to DVC was associated with this toxicity.[10] Schiller et al. also could not significantly correlate nausea and vomiting to dose to DVC and vestibular apparatus.[11]

DVC is not a visible discrete structure on a CT or an MRI scan; O'Steen and Amdur's[7] guidelines for contouring DVC have made the contouring reproducible and easy.

Even though causes for radiation-induced nausea and vomiting are multifactorial, the role of dose to DVC and vestibular apparatus has rather been controversial; nevertheless, studies have shown that elevated serotonin levels stimulate receptors adjacent to vagal afferent fibers in the brain stem.[12] Furthermore, the drugs recommended for the treatment for radiation-induced nausea and vomiting are 5-HT3 receptor antagonists.[13] Hence, making DVC one of those factors associated with nausea and vomiting, which could be readily omitted if the dose received by it is paid more attention while treatment planning.


  Conclusions Top


Even though our study did not conclusively show a connective link between dose to DVC or vestibular bodies and nausea, our study offers an opening rationale for an attempt to spare the DVC prospectively.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
The Italian Group for Antiemetic Research in Radiotherapy. Radiation induced emesis: A prospective observational multicenter Italian trial. Int J Radiat Oncol Biol Phys 1999;44:619-25.  Back to cited text no. 1
    
2.
Fan JW, Rosenthal DI, Morrison WH. Nausea, vomiting, and other unanticipated toxicities during intensity modulated radiation therapy (IMRT) for head and neck squamous cell cancer (HNSCC). Int J Radiat Oncol Biol Phys 2011;79:420e-8e.   Back to cited text no. 2
    
3.
Miller AD, Leslie RA. The area postrema and vomiting. Front Neuroendocrinol 1994;15:301-20.  Back to cited text no. 3
    
4.
Monroe AT, Reddy SC, Peddada AV. Dorsal vagal complex of the brainstem: Conformal avoidance to reduce nausea. Pract Radiat Oncol 2014;4:267-71.  Back to cited text no. 4
    
5.
Lee VH, Ng SC, Leung TW, Au GK, Kwong DL. Dosimetric predictors of radiation-induced acute nausea and vomiting in IMRT for nasopharyngeal cancer. Int J Radiat Oncol Biol Phys 2012;84:176-82.  Back to cited text no. 5
    
6.
Young YH, Ko JY, Sheen TS. Postirradiation vertigo in nasopharyngeal carcinoma survivors. Otol Neurotol 2004;25:366-70.  Back to cited text no. 6
    
7.
O'Steen L, Amdur RJ. An approach to contouring the dorsal vagal complex for radiotherapy planning. Med Dosim 2016;41:7-8.  Back to cited text no. 7
    
8.
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.  Back to cited text no. 8
    
9.
Wang TJ, Fontenla S, McCann P, Young RJ, McNamara S, Rao S, et al. Correlation of planned doseto area postrema and dorsal vagal complex with clinical symptoms of nausea and vomiting in a series of oropharyngeal cancer (OPC) patients treated with radiation alone using IMRT. Int J Radiat Oncol Biol Phys 2013;84:S467.  Back to cited text no. 9
    
10.
Ciura K, McBurney M, Nguyen B, Pham M, Rebueno N, Fuller CD, et al. Effect of brain stem and dorsal vagus complex dosimetry on nausea and vomiting in head and neck intensity-modulated radiation therapy. Med Dosim 2011;36:41-5.  Back to cited text no. 10
    
11.
Schiller K, Specht HM, Haller B, Hallqvist D, Devecka M, Becker von Rose A, et al. Correlation between delivered radiation doses to the brainstem or vestibular organ and nausea & vomiting toxicity in patients with head and neck cancers-an observational clinical trial. Radiat Oncol 2017;12:113.  Back to cited text no. 11
    
12.
Endo T, Minami M, Hirafuji M, Ogawa T, Akita K, Nemoto M, et al. Neurochemistry and neuropharmacology of emesis-the role of serotonin. Toxicology 2000;153:189-201.  Back to cited text no. 12
    
13.
Maranzano E, Feyer PCh, Molassiotis A, Rossi R, Clark-Snow RA, Olver I, et al. Evidence-based recommendations for the use of antiemetics in radiotherapy. Radiother Oncol 2005;76:227-33.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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