Original Research

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

Fed Pract. 2023 May;40(1):S46-S52 | doi:10.12788/fp.0344

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

Results

The VA Cancer Registry identified 113 patients treated for head and neck cancer during the study period. Of these, 55 patients met the inclusion criteria. No patients were lost to follow-up. The median follow-up was 29 months. The median age was 67 years (range, 41-83) (Table 1).

Oropharyngeal cancer was the most common primary site, accounting for 36 patients (65%).

All patients were treated with intensity-modulated radiotherapy. Patients treated with a sequential boost had an initial dose of 54 Gy and/or 50 Gy, followed by a boost to a total of 70 Gy at 2 Gy per fraction. Patients treated with a simultaneous integrated boost (SIB) technique received 70.0 Gy in 33 fractions, with elective volumes treated to 54.5 Gy in 33 fractions. Both patients with nasopharyngeal cancer were treated with SIB plans and had an intermediate dose volume of 59.4 Gy.

Systemic therapy was weekly cisplatin in 41 patients (75%) and cetuximab in 14 (25%). Twenty percent of patients receiving cisplatin switched to an alternative agent during treatment, most commonly carboplatin.

Forty-nine patients (89%) had a G-tube placed before starting radiation. G-tubes were in place for an interval of 0 to 47 months (mean, 8.6); 12 (22%) had a G-tube > 12 months. After completion of radiation, 18 patients (33%) had an abnormal MBS. These were done 1 to 50 months (mean, 14.8) after completion of radiation. Abnormal MBS occurred ≥ 12 months after radiation in 9 patients, 5 of whom had their G-tube in place for less than a year.

Forty-six patients (84%) survived more than 1 year and could be evaluated for late swallowing function. One-year dysphagia was seen in 17 (37%) of these patients. Recurrence was seen in 20 patients (36%), with locoregional recurrence in 12 (60%) of these cases. Recurrence occurred at a range of 0 to 15 months (mean, 5.6). Neither recurrence (P = .69) nor locoregional recurrence (P = .11) was associated with increased dysphagia at 1 year.

In patients who could be evaluated for long-term swallowing function, contralateral constrictor V60 ranged from 0% to 100% (median, 51%). V60 was < 40% in 18 patients (39%). With V60 < 40%, there was a 6% rate of 1-year dysphagia compared with 57% for V60 ≥ 40% (P < .001).

Patients with contralateral constrictor V60 < 40 and V60 ≥ 40 both had a mean age of 65 years. χ² analysis did not show a difference in T stage or systemic treatment but did show that patients with V60 < 40% were more likely to have N1 disease (P = .01), and less likely to have N2 disease (P = .01) compared with patients with V60 ≥ 40%. The difference in 1-year dysphagia between N0 to N1 patients (27%) and N2 to N3 patients (46%) was not statistically significant (P = .19).

In patients who could be evaluated for long-term swallowing function, the uninvolved pharynx volume median of the total constrictor volume was 32% (range, < 1%-62%). The uninvolved pharynx mean dose ranged from 28 to 68 Gy (median, 45). When the uninvolved pharynx mean dose was < 45 Gy, 1-year dysphagia was 22% compared with 52% with a dose ≥ 45 Gy (P = .03).

Table 2 compares constraints based on uninvolved pharynx with a constraint based on the contralateral constrictor.

Air cavity editing was performed in 27 patients (49%). One-year survival was 93% with air cavity editing, and 75% without, which was not statistically significant. Locoregional recurrence occurred in 3 patients (11%) with air cavity editing, and 9 (32%) without, which was not statistically significant. In patients surviving at least 1 year, contralateral constrictor V60 averaged 33% with editing and 62% without editing (P < .001). One-year dysphagia was 12% with air cavity editing and 67% without editing (P < .001).

An SIB technique was done in 26 patients (47%). One-year survival was 85% (n = 22) with SIB and 83% (n = 24) with sequential boost, which was not statistically significant. Locoregional recurrence occurred in 19% with SIB, and 32% with sequential boost, which was not statistically significant. For SIB patients alive at 1 year, the median contralateral V60 was 28%, compared with 66% for patients treated with sequential technique. Seventeen patients (77%) with SIB had V60 < 40%. Nineteen (86%) of SIB plans also had air cavity editing. One patient (5%) with SIB had dysphagia at 1 year compared with 16 (67%) sequential patients (P < .001).

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

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