Original Research

Contralateral Constrictor Dose Predicts Swallowing Function After Radiation for Head and Neck Cancer

Fed Pract. 2022 December;39(12):1-6 | doi:10.12788/fp.0344

Author(s):

Background: Radiation therapy can cause long-term dysphagia that seriously affects quality of life for survivors of head and neck cancer. This study evaluates a novel organ at risk, the contralateral pharyngeal constrictor muscles, to find out whether radiation dose to this structure predicts late swallowing function in patients with head and neck cancer.

Methods: The study included patients with head and neck cancer treated with radiation and concurrent systemic therapy at a single institution over 3 years. One-year dysphagia was defined as either the presence of a gastrostomy tube or an abnormal modified barium swallow ≥ 1 year after completion of radiation.

Results: Fifty-five patients met inclusion criteria, of which 46 were alive at 1 year. One-year dysphagia was present in 37% (n = 17) of this population. Contralateral constrictor V60 < 40% was associated with a 1-year dysphagia rate of 6%, compared with 57% in patients with V60 ≥ 40% (P < .001). An uninvolved pharynx mean dose < 45 Gy was associated with a 1-year dysphagia rate of 22%, compared with 52% in patients with an uninvolved pharynx mean dose ≥ 45 Gy (P = .03). Editing the clinical target volume off air cavities was associated with a decrease in 1-year dysphagia from 67% to 12% (P < .001), and with a reduction of contralateral constrictor V60 from 62% to 33% (P < .001). Air cavity editing was not associated with a change in locoregional recurrence or 1-year survival.

Conclusions: This is the first study to report a connection between contralateral constrictor dose and late swallowing function. The correlation between air cavity editing and contralateral constrictor V60 suggests that contralateral constrictor dose may depend partly on technique. Further studies are needed to explore whether these findings can be replicated prospectively and in other practice settings.

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References

2. Nguyen NP, Frank C, Moltz CC, et al. Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;61(3):772-778. doi:10.1016/j.ijrobp.2004.06.017

3. Ramaekers BLT, Joore MA, Grutters JPC, et al. The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy. Oral Oncol. 2011;47(8):768-774. doi:10.1016/j.oraloncology.2011.05.012

4. Christianen MEMC, Schilstra C, Beetz I, et al. Predictive modelling for swallowing dysfunction after primary (chemo)radiation: results of a prospective observational study. Radiother Oncol. 2012;105(1):107-114. doi:10.1016/j.radonc.2011.08.009

5. Vlachich G, Spratt DE, Diaz R, et al. Dose to inferior pharyngeal conctrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer. Radiother Oncol. 2014;110(3):435-440. doi:10.1016/j.radonc.2013.12.007

6. Mogadas S, Busch CJ, Pflug Cet al. Influence of radiation dose to pharyngeal constrictor muscles on late dysphagia and quality of life in patients with locally advanced oropharyngeal carcinoma. Strahlenther Onkol. 2020;196(6):522-529. doi:10.1007/s00066-019-01572-0

7. Caglar HB, Tishler RB, Othus M, et al. Dose to larynx predicts of swallowing complications after intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72(4):1110-1118. doi:10.1016/j.ijrobp.2008.02.048

8. Schwartz DL, Hutcheson K, Barringer D, et al. Candidate dosimetric predictors of long-term swallowing dysfunction after oropharyngeal intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(5):1356-1365. doi:10.1016/j.ijrobp.2009.10.002

9. Gensheimer MF, Nyflot M, Laramore GE, Laio JL, Parvathaneni U. Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy peg dependence in oropharynx cancer patients treated with split-neck IMRT technique. Radiat Oncol. 2015;11(1):1-7. doi:10.1186/s13014-016-0726-3

10. Hedström J, Tuomi L, Finizia C, Olsson C. Identifying organs at risk for radiation-induced late dysphagia in head and neck cancer patients. Clin Transl Radiat Oncol. 2019;19:87-95. doi:10.1016/j.ctro.2019.08.005

11. Bhide SA, Gulliford S, Kazi R, et al. Correlation between dose to the pharyngeal constrictors and patient quality of life and late dysphagia following chemo-IMRT for head and neck cancer. Radiother Oncol. 2009;93(3):539-544. doi:10.1016/j.radonc.2009.09.017

12. Caudell JJ, Schaner PE, Desmond RA, Meredith RF, Spencer SA, Bonner JA. Dosimetric factors associated with long-term dysphagia after definitive radiotherapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2010;76(2):403-409. doi:10.1016/j.ijrobp.2009.02.017

13. Levendag PC, Teguh DN, Voet P, et al. Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship. Radiother Oncol. 2007;85(1):64-73. doi:10.1016/j.radonc.2007.07.009

14. Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439. doi:10.1016/j.ijrobp.2004.05.050

15. Harari PM; NRG Oncology. Comparing high-dose cisplatin every three weeks to low-dose cisplatin weekly when combined with radiation for patients with advanced head and neck cancer. ClinicalTrials.gov identifier: NCT05050162. Updated November 25, 2022. Accessed December 7, 2022. https://clinicaltrials.gov/ct2/show/NCT05050162

16. Wang JJ, Goldsmith TA, Holman AS, Cianchetti M, Chan AW. Pharyngoesophageal stricture after treatment for head and neck cancer. Head Neck. 2011;34(7):967-973. doi:10.1002/hed.21842

17. Kendall KA, McKenzie SW, Leonard RJ, Jones CU. Timing of swallowing events after single-modality treatment of head and neck carcinoma with radiotherapy. Ann Otol Rhinol Laryngol. 2000;109(8, pt 1):767-775. doi:10.1177/000348940010900812

18. Ohmae Y, Ogura M, Kitahara S. Effects of head rotation on pharyngeal function during normal swallow. Ann Otol Rhinol Laryngol. 1998;107(4):344-348. doi:10.1177/000348949810700414

19. Spencer CR, Gay HA, Haughey BH, et al. Eliminating radiotherapy to the contralateral retropharyngeal and high level II lymph nodes in head and neck squamous cell carcinoma is safe and improves quality of life. Cancer. 2014;120(24):3994-4002. doi:10.1002/cncr.28938

Radiation therapy can cause long-term dysphagia that seriously affects quality of life for survivors of head and neck (H&N) cancer.^1-3 Numerous studies have linked pharyngeal constrictor dose to long-term dysphagia, but conclusions about the dose distribution that can be safely tolerated have been inconsistent. For example, a group from the Netherlands found that the mean dose to the superior pharyngeal constrictor muscle and the supraglottic larynx were each predictive of dysphagia.⁴ A subsequent Vanderbilt study refuted these findings, reporting that these structures were not predictive but that dose to the inferior pharyngeal constrictor muscle was.⁵ Other studies have connected late dysphagia with dose to the middle pharyngeal constrictor muscle, total larynx, oral cavity, contralateral submandibular gland, contralateral parotid gland, or a combination of these structures.^6-14 NRG Oncology trials commonly evaluate dose to the “uninvolved pharynx,” which is the total pharyngeal constrictor muscle volume minus the planning target volume for the lowest dose target volume. NRG H&N trials 3, 4, 5, 6, 8, and 9 all use uninvolved pharynx mean dose ≤ 45 Gy as a constraint to judge radiation plan quality.

Differences in methodology or patient population may explain the inconsistency of prior studies on dosimetric predictors of dysphagia, but it is possible that these studies did not evaluate the optimal metric for dysphagia. This study evaluates a novel organ at risk, the contralateral pharyngeal constrictor muscle, to determine whether dose to this structure is predictive of late swallowing function. The study also compares a constraint based on this structure to the NRG uninvolved pharynx constraint mentioned earlier.

Methods

This study is a retrospective review of patients treated at the Richard L. Roudebush Veterans Affairs (VA) Medical Center in Indianapolis, Indiana. Patients were identified by searching the VA Cancer Registry for patients treated for H&N squamous cell carcinoma between September 1, 2016, and August 30, 2019. Eligible sites included cancers of the nasopharynx, oropharynx, hypopharynx, larynx and oral cavity, as well as H&N cancer of an unknown primary site. Only patients treated with primary radiation with concurrent systemic therapy were included. Patients were excluded if they had prior surgery or radiation to the H&N.

The pharyngeal constrictor muscles were contoured per the techniques described by Bhide and colleagues.¹¹ The contralateral constrictor was defined as the half of the constrictor volume contralateral to the primary site. For midline tumors, the side of the neck with a lower volume of lymph node metastases was judged to be the contralateral side.

Air cavity editing was assessed by making an auto-expansion of the gross tumor volume (GTV) to match the boost volume clinical target value (CTV), then determining whether the size of this CTV was decreased in an air cavity on any axial slice. In patients with air cavity editing, the CTV was not completely cropped out of air, just reduced relative to the expansion used in soft tissue (Figure 1).

References

1. Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, et al. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol. 2008;26(22):3770-3776. doi:10.1200/JCO.2007.14.6647

2. Nguyen NP, Frank C, Moltz CC, et al. Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005;61(3):772-778. doi:10.1016/j.ijrobp.2004.06.017

3. Ramaekers BLT, Joore MA, Grutters JPC, et al. The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy. Oral Oncol. 2011;47(8):768-774. doi:10.1016/j.oraloncology.2011.05.012

4. Christianen MEMC, Schilstra C, Beetz I, et al. Predictive modelling for swallowing dysfunction after primary (chemo)radiation: results of a prospective observational study. Radiother Oncol. 2012;105(1):107-114. doi:10.1016/j.radonc.2011.08.009

5. Vlachich G, Spratt DE, Diaz R, et al. Dose to inferior pharyngeal conctrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer. Radiother Oncol. 2014;110(3):435-440. doi:10.1016/j.radonc.2013.12.007

6. Mogadas S, Busch CJ, Pflug Cet al. Influence of radiation dose to pharyngeal constrictor muscles on late dysphagia and quality of life in patients with locally advanced oropharyngeal carcinoma. Strahlenther Onkol. 2020;196(6):522-529. doi:10.1007/s00066-019-01572-0

7. Caglar HB, Tishler RB, Othus M, et al. Dose to larynx predicts of swallowing complications after intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72(4):1110-1118. doi:10.1016/j.ijrobp.2008.02.048

8. Schwartz DL, Hutcheson K, Barringer D, et al. Candidate dosimetric predictors of long-term swallowing dysfunction after oropharyngeal intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(5):1356-1365. doi:10.1016/j.ijrobp.2009.10.002

9. Gensheimer MF, Nyflot M, Laramore GE, Laio JL, Parvathaneni U. Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy peg dependence in oropharynx cancer patients treated with split-neck IMRT technique. Radiat Oncol. 2015;11(1):1-7. doi:10.1186/s13014-016-0726-3

10. Hedström J, Tuomi L, Finizia C, Olsson C. Identifying organs at risk for radiation-induced late dysphagia in head and neck cancer patients. Clin Transl Radiat Oncol. 2019;19:87-95. doi:10.1016/j.ctro.2019.08.005

11. Bhide SA, Gulliford S, Kazi R, et al. Correlation between dose to the pharyngeal constrictors and patient quality of life and late dysphagia following chemo-IMRT for head and neck cancer. Radiother Oncol. 2009;93(3):539-544. doi:10.1016/j.radonc.2009.09.017

12. Caudell JJ, Schaner PE, Desmond RA, Meredith RF, Spencer SA, Bonner JA. Dosimetric factors associated with long-term dysphagia after definitive radiotherapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2010;76(2):403-409. doi:10.1016/j.ijrobp.2009.02.017

13. Levendag PC, Teguh DN, Voet P, et al. Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship. Radiother Oncol. 2007;85(1):64-73. doi:10.1016/j.radonc.2007.07.009

14. Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425-1439. doi:10.1016/j.ijrobp.2004.05.050

15. Harari PM; NRG Oncology. Comparing high-dose cisplatin every three weeks to low-dose cisplatin weekly when combined with radiation for patients with advanced head and neck cancer. ClinicalTrials.gov identifier: NCT05050162. Updated November 25, 2022. Accessed December 7, 2022. https://clinicaltrials.gov/ct2/show/NCT05050162

16. Wang JJ, Goldsmith TA, Holman AS, Cianchetti M, Chan AW. Pharyngoesophageal stricture after treatment for head and neck cancer. Head Neck. 2011;34(7):967-973. doi:10.1002/hed.21842

17. Kendall KA, McKenzie SW, Leonard RJ, Jones CU. Timing of swallowing events after single-modality treatment of head and neck carcinoma with radiotherapy. Ann Otol Rhinol Laryngol. 2000;109(8, pt 1):767-775. doi:10.1177/000348940010900812

18. Ohmae Y, Ogura M, Kitahara S. Effects of head rotation on pharyngeal function during normal swallow. Ann Otol Rhinol Laryngol. 1998;107(4):344-348. doi:10.1177/000348949810700414

19. Spencer CR, Gay HA, Haughey BH, et al. Eliminating radiotherapy to the contralateral retropharyngeal and high level II lymph nodes in head and neck squamous cell carcinoma is safe and improves quality of life. Cancer. 2014;120(24):3994-4002. doi:10.1002/cncr.28938

Contralateral Constrictor Dose Predicts Swallowing Function After Radiation for Head and Neck Cancer

References

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